ENGINEERED MESENCHYMAL STROMAL CELLS C _{ROSS-REFERENCE TO RELATED APPLICATIONS} This application claims the benefit of U.S. Patent Application Serial No.63/421,832, filed on November 2, 2022. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “07039-2165WO1.xml.” The XML file, created on October 31, 2023, is 160,000 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. T ^{ECHNICAL FIELD} This document relates to methods and materials for using engineered mesenchymal stromal cells (MSCs) to treat a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases (e.g., graft-versus- host disease (GVHD)). For example, this document provides CAR-MSCs (e.g., MSCs expressing a chimeric antigen receptor (CAR) having the ability to bind to a tissue-specific antigen) having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or one or more trafficking polypeptides. Such CAR-MSCs can exert an immunosuppressive effect (e.g., can reduce or eliminate an immune response such as an overactive immune response) in a targeted tissue. This document also provides methods for administering one or more CAR-MSCs having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) to treat the mammal. ^{BACKGROUND INFORMATION} MSCs are an attractive cell therapy candidate due to their trophic abilities allowing for homing to sites of inflammation (Shi et al., Nat. Rev. Nephrol., 14:493-507 (2018)) and immunomodulatory functions supporting immune homeostasis (Uccelli et al., Nat. Rev. Immunol., 8:726-736 (2008)). However, reliable therapeutic efficacy has not been demonstrated in human clinical trials, making MSCs the most studied experimental cell therapy platform in the world with no resultant US FDA-approved therapies (Murata et al., Bone Marrow Transplant., 56:2355-2366 (2021)). MSC therapeutic efficacy in humans is limited by several factors including 1) suboptimal immunosuppression and 2) insufficient homing to target sites once administered. Strategies to individually address these shortcomings with cytokine modulation (Guess et al. Stem Cells Transl. Med., 6:1868-1879 (2017)), manipulation of MSC extracellular vesicles (Harrell et al., Cells, 8(2019)), and genetic modification (Sarkar et al., Blood 118:e184-191 (2011)), have been attempted, but have yet to simultaneously enhance both immunosuppression and homing capacity. SUMMARY This document provides methods and materials involved in treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD). For example, one or more CAR-MSCs having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can be administered to a mammal to induce an immunosuppressive response (e.g., to reduce or eliminate an inflammatory immune response) in a targeted tissue within the mammal. In some cases, one or more CAR-MSCs having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can be administered (e.g., by adoptive transfer) to a mammal (e.g., a human) having (or at risk of developing) one or more autoimmune diseases (eg GVHD) to treat the mammal As demonstrated herein CAR-MSCs having elevated levels of a nuclear factor kappa B subunit 1 (NFkB1) polypeptide, a Jun proto- oncogene (JUN) polypeptide, a transcription factor RelB (RELB) polypeptide, an interferon regulatory factor 1 (IRF1) polypeptide, a tumor necrosis factor (TNF) ? polypeptide, an interleukin (IL)-10 polypeptide, a fibroblast growth factor (FGF)-2 polypeptide, a granulocyte colony stimulating factor (G-CSF) polypeptide, a granulocyte-macrophage colony-stimulating factor (GM-CSF) polypeptide, an eotaxin polypeptide, a galectin 9 (Gal- 9) polypeptide, a programmed cell death protein 1 (PD-1) polypeptide, a T-cell immunoglobin mucin-3 (TIM-3) polypeptide, a CXC chemokine receptor (CXCR) 3 polypeptide, and/or a CXCR4 polypeptide exhibited both enhanced immunosuppression and enhanced homing capacity to sites of inflammation. Also as demonstrated herein, CAR- MSCs having elevated levels of a cytotoxic T-lymphocyte-associated-protein 4 (CTLA4) polypeptide, a toll-like receptor (TLR) 3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and/or a TNF receptor 2 (TNFR2) polypeptide exhibited both enhanced immunosuppression and enhanced homing capacity to sites of inflammation. In general, one aspect of this document features a MSC including (1) exogenous nucleic acid encoding a CAR targeting an epithelial-specific antigen, where the MSC expresses the CAR, and (2) an elevated level of a polypeptide selected from the group consisting of a NFkB1 polypeptide, a JUN polypeptide, a RELB polypeptide, an IRF1 polypeptide, a TNFα polypeptide, an IL-10 polypeptide, a FGF-2 polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, an eotaxin polypeptide, a Gal-9 polypeptide, a PD-1 polypeptide, a TIM-3 polypeptide, a CXCR3 polypeptide, a CXCR4 polypeptide, a CTLA4 polypeptide, a TLR3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and a TNFR2 polypeptide. The MSC can be a human MSC. The MSC can be an adipose derived-MSC. The epithelial-specific antigen can be E-cadherin (Ecad). The polypeptide can be the NFkB1 polypeptide, the JUN polypeptide, the RELB polypeptide, or the IRF1 polypeptide. The MSC can include exogenous nucleic acid encoding the NFkB1 polypeptide, where the MSC expresses the NFkB1 polypeptide. The MSC can include exogenous nucleic acid encoding the JUN polypeptide, where the MSC expresses the JUN polypeptide. The MSC can include exogenous nucleic acid encoding the RELB polypeptide, where the MSC expresses the RELB polypeptide The MSC can include exogenous nucleic acid encoding the IRF1 polypeptide, where the MSC expresses the IRF1 polypeptide. The polypeptide can be the CXCR3 polypeptide or the CXCR4 polypeptide. The MSC can include exogenous nucleic acid encoding the CXCR3 polypeptide, where the MSC expresses the CXCR3 polypeptide. The MSC can include exogenous nucleic acid encoding the CXCR4 polypeptide, where the MSC expresses the CXCR4 polypeptide. The polypeptide can be the PD-1 polypeptide, the Gal-9 polypeptide, or the TIM-3 polypeptide. The MSC can include exogenous nucleic acid encoding the PD-1 polypeptide, where the MSC expresses the PD-1 polypeptide. The MSC can include exogenous nucleic acid encoding the Gal-9 polypeptide, where the MSC expresses the Gal-9 polypeptide. The MSC can include exogenous nucleic acid encoding the TIM-3 polypeptide, where the MSC expresses the TIM-3 polypeptide. The polypeptide can be the TNFα polypeptide, the IL-10 polypeptide, or the FGF-2 polypeptide. The MSC can include exogenous nucleic acid encoding the TNFα polypeptide, where the MSC expresses the TNFα polypeptide. The MSC can include exogenous nucleic acid encoding the IL-10 polypeptide, where the MSC expresses the IL-10 polypeptide. The MSC can include exogenous nucleic acid encoding the FGF-2 polypeptide, where the MSC expresses the FGF- 2 polypeptide. The CAR can include a heavy chain comprising the CDRs set forth in SEQ ID NO:1, and a light chain comprising the CDRs set forth in SEQ ID NO:2. The heavy chain can include an amino acid sequence set forth in SEQ ID NO:1, and where the light chain can include an amino acid sequence set forth in SEQ ID NO:2. The CAR can include a heavy chain comprising the CDRs set forth in SEQ ID NO:3, and a light chain comprising the CDRs set forth in SEQ ID NO:4. The heavy chain can include an amino acid sequence set forth in SEQ ID NO:3, and where the light chain can include an amino acid sequence set forth in SEQ ID NO:4. In another aspect, this document features compositions including a MSC including (1) exogenous nucleic acid encoding a CAR targeting an epithelial-specific antigen, where the MSC expresses the CAR, and (2) an elevated level of a polypeptide selected from the group consisting of a NFkB1 polypeptide, a JUN polypeptide, a RELB polypeptide, an IRF1 polypeptide, a TNFα polypeptide, an IL-10 polypeptide, a FGF-2 polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, an eotaxin polypeptide, a Gal-9 polypeptide, a PD-1 polypeptide a TIM 3 polypeptide a CXCR3 polypeptide a CXCR4 polypeptide a CTLA4 polypeptide, a TLR3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and a TNFR2 polypeptide. In another aspect, this document features methods for treating a mammal having GVHD. The methods can include, or consist essentially of, administering to a mammal having GVHD a MSC including (1) exogenous nucleic acid encoding a CAR targeting an epithelial-specific antigen, where the MSC expresses the CAR, and (2) an elevated level of a polypeptide selected from the group consisting of a NFkB1 polypeptide, a JUN polypeptide, a RELB polypeptide, an IRF1 polypeptide, a TNFα polypeptide, an IL-10 polypeptide, a FGF-2 polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, an eotaxin polypeptide, a Gal-9 polypeptide, a PD-1 polypeptide, a TIM-3 polypeptide, a CXCR3 polypeptide, a CXCR4 polypeptide, a CTLA4 polypeptide, a TLR3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and a TNFR2 polypeptide. The mammal can be a human. The symptom of the GVHD can be reduced at least 10 percent. The number of Tregs within the mammal can be increased at least 10 percent. In another aspect, this document features methods for suppressing an immune response within a mammal. The methods can include, or consist essentially of, administering to a mammal a MSC including (1) exogenous nucleic acid encoding a CAR targeting an epithelial-specific antigen, where the MSC expresses the CAR, and (2) an elevated level of a polypeptide selected from the group consisting of a NFkB1 polypeptide, a JUN polypeptide, a RELB polypeptide, an IRF1 polypeptide, a TNFα polypeptide, an IL-10 polypeptide, a FGF-2 polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, an eotaxin polypeptide, a Gal-9 polypeptide, a PD-1 polypeptide, a TIM-3 polypeptide, a CXCR3 polypeptide, a CXCR4 polypeptide, a CTLA4 polypeptide, a TLR3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and a TNFR2 polypeptide. The mammal can be a human. The number of activated T cells within the mammal can be reduced at least 10 percent. The number of Tregs within the mammal can be increased at least 10 percent. In another aspect, this document features methods for reducing the number of activated T cells within a mammal. The methods can include, or consist essentially of, administering to a mammal a MSC including (1) exogenous nucleic acid encoding a CAR targeting an epithelial specific antigen where the MSC expresses the CAR and (2) an elevated level of a polypeptide selected from the group consisting of a NFkB1 polypeptide, a JUN polypeptide, a RELB polypeptide, an IRF1 polypeptide, a TNFα polypeptide, an IL-10 polypeptide, a FGF-2 polypeptide, a G-CSF polypeptide, a GM-CSF polypeptide, an eotaxin polypeptide, a Gal-9 polypeptide, a PD-1 polypeptide, a TIM-3 polypeptide, a CXCR3 polypeptide, a CXCR4 polypeptide, a CTLA4 polypeptide, a TLR3 polypeptide, a TLR4 polypeptide, a TLR9 polypeptide, and a TNFR2 polypeptide. The mammal can be a human. The number of activated T cells within the mammal can be reduced at least 10 percent. The number of Tregs within the mammal can be increased at least 10 percent. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF THE DRAWINGS Figures 1A-1J show that MSCs are stably transduced to express CAR and that EcCAR-MSCs exhibit superior T cell suppression compared to untransduced (UTD) MSCs. Figure 1A is a representative flow cytometry plot depicting the expression of CAR19 as detected by goat anti-mouse IgG (y-axis) following transduction of MSCs with VSV-? lentiviral particles with increasing concentration of protamine sulfate enhancer (50 µg/mL and 100 µg/mL). Data are representative of >3 independent experiments using 5 different biological MSC donors. Figure 1B is a histogram showing CAR expression of anti-Ecad CAR-MSC (EcCAR-MSC), anti-CD103 T cell integrin CAR-MSC (CD103CAR-MSC), and anti-CD19 CAR MSC (CD19CAR-MSC) positive control as detected by flow cytometry using goat anti-mouse IgG antibody. Data shown are mean +/- s.d. representative of at > 6 independent experiment using 5 MSC donors. Figure 1C is a graph showing CAR expression of EcCAR-MSC compared to UTD-MSC by flow cytometry 2 days and 11 days following transduction with multiple cell passages. Data shown are mean +/- standard deviation (s.d.) representative of 3 independent experiments using 3 MSC donors. Statistical analysis was performed by 2-way ANOVA (**** p ≤ 0.0001) (n = 3 per group). Figure 1D is a histogram depicting > 90% expression of Ecad-CAR (EcCAR) on MSCs across 3 different primary biological donors. Data are representative of >10 independent experiments using 5 different biological MSC donors. The x axis represents the level of detection of CAR by goat anti- mouse within the APC channel of the flow cytometry instrument. Figure 1E is a graph of flow cytometry-based quantification of absolute CD3 ⁺ cells following a co-culture of EcCAR-MSCs, UTD-MSCs, or no MSCs with activated T cells at 1:5 and 1:10 MSC:T cell ratio. Data shown are mean +/- s.d. using 3 MSC donors. Statistical analysis was performed by 2-way ANOVA (* p ≤ 0.05, **** p < 0.0001) (n = 3 per group). Figure 1F is a graph of flow cytometry-based quantification of absolute CD3 ⁺ cells following a co-culture of EcCAR-MSCs, UTD-MSCs, or no MSCs with activated T cells, in the presence of media alone or soluble Ecad at 250 ng/mL. Data shown are mean +/- s.d. of representative experiments using 5 MSC donors. Statistical analysis was performed by 2-way ANOVA (no significant (ns) = p ≥ 0.05, **p ≤ 0.01) (n = 2 per group). Figure 1G is a graph of flow cytometry-based quantification of absolute CD3 ⁺ cells following co-culture of EcCAR- MSCs, UTD-MSCs, or no MSCs with activated T cells, in the presence of the irradiated Ecad positive cell line MCF-7, enhanced T cell suppression with antigen specific activation. Data shown are mean +/- s.d. of representative experiments using 3 different biological MSC donors. Statistical analysis was performed by 2-way ANOVA (ns = p ≥ 0.05, *p ≤ 0.05) (n = 2 per group). Figure 1H is a graph showing the stemness immuno-phenotype of UTD-MSCs and EcCAR-MSCs measured with flow cytometry after staining MSCs for CD105, CD90, CD73, CD34, CD45, and CD14. Data shown are mean +/- s.d. of 4 independent experiments from 4 biological MSC donors. Statistics were performed by 2-way ANOVA (ns = p ≥ 0.05) (n = 3 per group). Figures 1I-1J contain graphs of bulk RNAseq analysis of upregulated (Figure 1I) and downregulated (Figure 1J) pathways in EcCAR MSCs as compared to UTD MSC by CellMarker Augmented gene set enrichment analysis. Significant genes were selected by > 1 or < -1 log fold change and < 0.05 adjusted p values via differential expression analysis of 3 biological replicates per group. Calculated -log10 p value displayed on x-axis to represent statistically significant enrichment for all pathways -log10 (p < 0.05). Data representing analysis of 3 different biological MSC donors per differential expression analysis group. Figures 2A-2H show that EcCAR-MSCs suppress T cell activity in tumor and GVHD models. Figure 2A is a schematic of an exemplary method for evaluating the effect of EcCAR-MSCs on a Nalm6 xenograft tumor model. Immunocompromised NOD-SCID-? ^-/- (NSG) mice were engrafted with luciferase ⁺ CD19 ⁺ Nalm6 cells (1 x 10 ⁶ intravenously (i.v.)). Bioluminescent imaging was performed 5 days later to confirm engraftment. All mice were then treated with CD19-targeted CAR T (CART19) cells (1 x 10 ⁶ cells i.v.) and irradiated Ecad ⁺ cell line MCF-7. Mice were additionally randomized to treatment with UTD-MSCs or EcCAR-MSCs (1 x 10 ⁶ cells intraperitoneally (i.p.)). Mice were then followed biweekly for bioluminescent imaging and monitored for survival. Figure 2B is a graph of tumor flux following CART19 infusion in Nalm6 model, comparing EcCAR-MSCs, UTD-MSCs, and no treatment. Data shown are mean +/- standard error of the mean (SEM) with statistical analysis by 2-way ANOVA (**p ≤ 0.01, ***p ≤ 0.001, ns = p ≥ 0.05) (n = 3-4 mice per group). Figure 2C is a graph of survival outcomes of EcCAR-MSC compared to UTD-MSC and no MSC control. Statistical analysis was performed by Kaplan-Meier Simple survival analysis (*p ≤ 0.05, ns = p ≥ 0.05) (n = 3-4 mice per group). Figure 2D is a schematic of an exemplary method for evaluating the effect of EcCAR-MSCs in a GVHD Xenograft mouse model. Human PBMCs were injected (25-30 x 10 ⁶ cells i.v.) into NSG mice along with either EcCAR-MSCs or UTD-MSCs (1 x 10 ⁶ cells i.p. on days 0, 14, and 28). Mice were then monitored for weight loss, the development of clinical signs of GVHD (scored based on weight loss, diarrhea, posture, activity, fur texture, and skin integrity), and survival. Figure 2E is a graph of percent weight change from baseline in GVHD xenografts following treatment with UTD-MSCs, EcCAR-MSCs, or no treatment. Data shown are mean +/- s.d. with statistical analysis performed by 2-way ANOVA (****p ≤ 0.0001, ns = p ≥ 005) (n = 5 mice per group) Figure 2F contains representative mouse images (right) and a graph (left) of GVHD clinical scoring results from day 50 on following treatment with EcCAR-MSC, UTD-MSC, or no MSCs, with. Data shown are mean +/- s.d. with statistical analysis performed by 2-way ANOVA **p ≤ 0.01, ns = p ≥ 0.05) (n = 5 mice per group). Figure 2G is a graph of a mouse peripheral blood assessment comparing absolute number of human CD3 ⁺ T cells between EcCAR-MSC and UTD-MSC treatment groups by flow cytometry 2 weeks following first MSC injection. Data shown are mean +/- s.d. with statistical analysis performed by unpaired t-test (**p≤0.01) (n = 5 mice per group). Figure 2H is a graph of survival outcomes following treatment with EcCAR-MSCs compared to UTD- MSCs and no MSC control. Statistical analysis was performed by Kaplan-Meier Simple survival analysis (**p ≤ 0.01, ns = p ≥ 0.05) (n ≥ 5 mice per group). Tumor figures (Figures 2A-2C) are representative of 2 independent experiments on 2 different tumor models and 2 different biological MSC donors. GVHD figures (Figures 2D-2H) are representative of 3 independent experiments on 3 different biological PBMC donors and 3 different biological MSC donors performed on both male and female NSG mice. Figures 3A-3E show that RNAseq analyses revealed antigen specific activation of EcCAR-MSCs leading to enrichment of immunosuppressive pathways. Figure 3A is a heat map depicting the distinct gene expression profile of EcCAR-MSC+Ecad samples highlighting the functional impact of CAR antigen-specific stimulation through hierarchical clustering with unstimulated EcCAR-MSC, stimulated UTD-MSC+Ecad, and unstimulated UTD-MSC samples. Displaying gene fold counts normalized across all samples (padj ? 0.05) (n = 3 MSC donors per condition). Figure 3B is a PCA depicting RNAseq transcript profiles of 6 samples from 3 biological MSC replicates indicating clustering solely by donor in unstimulated UTD-MSCs and stimulated UTD-MSCs. Figure 3C is a PCA of unstimulated and stimulated EcCAR-MSCs revealing unique clustering by stimulation group indicating CAR based functional activation. Figure 3D uses Ingenuity Pathway Analysis (IPA) to reveal upregulated canonical pathways in stimulated vs. unstimulated EcCAR-MSCs. Dashed line marking significantly enriched pathways (p?0.05) (n=3 donors per group). Figure 3E contains graphs of a normalized gene count comparisons across unstimulated UTD-MSC, stimulated UTD-MSC, unstimulated EcCAR-MSC, and stimulated EcCAR-MSC showing activation of CAR(CD28) linked transcription factor genes NFkB1 JUN RELB and IRF1 in stimulated EcCAR-MSCs. Data shown are mean +/- s.d. of normalized gene counts across groups. Statistical analysis was performed by 1-way ANOVA (**p≤0.01, ***p≤ 0.001, ****p≤0.0001) (n = 3 donors per group). Figures 4A-4I show that EcCAR-MSCs support enhanced immunosuppression through increased secretion of cytokines, T cell mediation, and upregulation of inhibitory surface markers. Figure 4A contains graphs of serum cytokines levels in pg/mL of IL-10 polypeptides, TNFα polypeptides, G-CSF polypeptides, Eotaxin polypeptides, and FGF-2 polypeptides in EcCAR-MSC treated mice as compared to UTD-MSC, and untreated xenografts by multiplex assay 17 days following administration. Data shown are mean +/- SEM with statistical analysis performed by ordinary 1-way ANOVA (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001) (n = 4-6 samples per group). Figure 4B is a graph of human T cell subsets in EcCAR-MSC vs. UTD-MSC treated mice from GVHD xenografts. Quantification of human CD4 ⁺ and CD8 ⁺ T cell suppression are depicted by absolute cell counts within peripheral mouse blood 2 weeks following first MSC injection by flow cytometry. Data shown are mean +/- s.d. of the absolute number of cell subsets. Statistical analysis was performed by 2-way ANOVA (*p ≤ 0.05, ***p ≤ 0.001) (n = 5 per group). Figure 4C is a graph of human CD4 ⁺ to CD8 ⁺ T cell proportions by flow cytometry in mice treated with EcCAR-MSCs compared to UTD-MSCs in GVHD xenografts. Data shown are mean +/- s.d. of percent of cell subsets. Statistical analysis was performed by 2-way ANOVA (**p ≤ 0.01) (n = 5 per group). Figure 4D is a graph correlating percent weight change in GVHD mice from baseline day 0 to day 31 showing significant amelioration of weight loss and prevention of GVHD in EcCAR-MSC treated mice only. Data shown are mean +/- SEM of percent weight change. Statistical analysis was performed by 2-way ANOVA (***p ≤ 0.001) (n = 5 per group). Figure 4E is a graph of human CD4 ⁺ , CD25 ⁺ , and CD127- Treg-like cell subset 4 weeks following PBMC administration with MSC treatment. Flow cytometry analysis revealed a significant increase in Treg % within EcCAR-MSC treated mice as compared to UTD-MSC. Data shown are mean +/- s.d. of cell subset percentages Statistical analysis was performed by unpaired t-test (***p≤ 0.001) (n = 4 per group). Figure 4F is a T- distributed stochastic neighbor embedding (tSNE) plot of surface marker expression by flow cytometry time of flight (CyTOF) of Ecad stimulated and unstimulated EcCAR MSCs and UTD-MSCs. Ecad stimulation was induced via Ecad ⁺ irradiated cell line MCF7 for 24 hours prior to CyTOF analysis. tSNE plot of surface marker landscape within samples with unsupervised clustering revealed the presence of 4 major cell populations: Ecad ⁺ Cell Line, UTD-MSC, EcCAR-MSCs, and Ecad stimulated EcCAR-MSCs. Figure 4G is a heat map displaying cluster surface characterization with CXCR3 and PD1 markers uniquely characterizing stimulated EcCAR-MSC population cluster. Figure 4H is a graph of the percent of the expression of inhibitory receptor surface markers PD-1 and Gal-9 analyzed by flow cytometry in UTD-MSCs and EcCAR-MSCs stimulated with soluble Ecad and cocultured with PBMCs for 5 days before surface marker assessment. Figure 4I is a graph of the percent of the expression of migratory chemokine surface markers CXCR3 and CXCR4 analyzed by flow cytometry in UTD-MSCs and EcCAR-MSCs stimulated with soluble Ecad and cocultured with PBMCs for 5 days before surface marker assessment. Data shown in Figures 4H-4I are mean +/- s.d. % surface expression representing 3 MSC donors. Statistical analysis was performed by 2-way ANOVA (**p ≤ 0.01, ****p ≤ 0.0001) (n = 3 per group). Figures 5A-5G show EcCAR-MSC homing and safety profiles within in vivo canine and murine models. Figure 5A is a schematic of an exemplary method for CAR-MSC manufacturing, safety, and homing analysis for in vivo healthy canine models. Figure 5B contains an exemplary immunohistochemical (IHC) analysis of a transverse colon histology stained for Ecad 3 days following EcCAR-MSC administration indicating homing of human EcCAR-MSCs to canine Ecad ⁺ rich tissues. Human CD105 positive antibody (top) and canine Ecad positive antibody (bottom) appear colocalized via IHC analysis at various magnifications in canine colon tissue. Figure 5C contains graphs of complete blood count levels following the i.p. administration of EcCAR-MSCs. This includes, from left to right, white blood cells (WBCs), monocytes, lymphocytes, neutrophils, and platelets with short term (3 day) and long term (28 day) blood level monitoring following in vivo EcCAR-MSC injection as compared to baseline. Data shown are mean +/- s.d. of blood composition with statistical analysis performed by 2-way ANOVA (ns = p ≥ 0.05 between groups) (n = 3 per experimental group). Figure 5D contains graphs, from left to right, of total protein, BUN, creatinine, albumin, and alkaline phosphatase levels with short term (3 day) and long term (28 day) monitoring following in vivo EcCAR MSC injection Data shown are mean +/ sd of blood composition with statistical analysis performed by 2-way ANOVA (ns = p ≥ 0.05). Figure 5E is a schematic of an exemplary method for determining the expansion kinetics and persistence of CAR-MSCs in vivo using a luciferase positive MSC xenograft model. Luciferase expressing UTD-MSC or CAR-MSCs were injected into human PBMC-primed NSG mice with or without irradiated Ecad ⁺ MCF7 cells as a form of CAR stimulation. Mice were followed by serial bioluminescent imaging on daily basis. Figure 5F is a graph of the flux of bioluminescent imaging as a measure of MSC expansion and clearance kinetics following administration of EcCAR-MSC or UTD-MSC with or without Ecad stimulation. Figure 5G is an exemplary image of luciferase-positive MSC expansion and clearance in mice from 3 to 24 days following administration. Data shown are mean +/- standard deviation (s.d.) with statistical analysis performed by 2-way ANOVA (ns = p ≥ 0.05) (n = 5 per group). Figure 6 shows the canine/human cross reactivity of a luciferase canine Ecad ⁺ MCKD cell line co-cultured with human versus mouse versus canine directed Ecad CAR T cells. Bioluminescent imaging was taken after 24 hours of co-culturing. UTD = untransduced. Figure 7 shows a schematic of an exemplary EcCAR-MSC construct where hmcECAD.6 represents human, mouse, and canine cross-reactive Ecad antigen binding domain. Figure 8A is a schematic of an exemplary method for evaluating the effect of EcCAR-MSCs on JeKo1 cell xenograft tumor model. JeKo1 cells were injected (1 x 10 ⁶ cells i.v.) into NSG mice along with either EcCar-MSCs or UTD-MSCs (1 x 10 ⁶ cells i.p. on days 0, 14, and 28). Mice were then monitored for weight loss, the development of clinical signs of GVHD (scored based on weight loss, diarrhea, posture, activity, fur texture, and skin integrity), and survival. Figure 8B is a graph of the tumor flux (photons/sec) of NSG mice injected with JeKo1 cells. Figure 9A is a graph of differentially expressed genes in unstimulated EcCAR-MSC vs. UTD-MSC, Ecad-stimulated vs. unstimulated EcCAR-MSCs, and Ecad-stimulated vs. unstimulated UTD-MSCs. Data display unregulated and downregulated gene counts within comparisons with adj. p value < 0.01 and ± 1-log fold change. Transcriptional alterations induced by Ecad stimulation of CAR MSCs included 2362 significant genes vs EcCAR MSC alone and 3032 significant genes vs. Ecad stimulated UTD-MSCs. Transcriptional alterations induced by CAR transduction included 606 significant genes. Transcriptional alterations induced by Ecad stimulation included 206 significant genes. Figure 9B shows that Ingenuity Pathway Analysis (IPA) revealed upregulated canonical pathways in unstimulated EcCAR-MSCs vs. UTD-MSCs. The dashed line marks enriched pathways (p ≤ 0.05) (n=3 MSC donors per group). Figure 10 contains graphs of, from left to right, MDC polypeptides, GRO polypeptides, GM-CSF polypeptides, MCP-3 polypeptides, and Flt-3 polypeptides in EcCAR-MSC treated mice as compared to UTD-MSC, and untreated xenografts by multiplex assay 17 days following administration. Data shown are mean +/- SEM with statistical analysis performed by ordinary 1-way ANOVA (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ? 0.0001) (n = 4-6 samples per group). Figure 11 is a heat map of the clustering of surface marker expression in populations of cells identified by CyTOF constituting cell clusters from Figure 4F. Figure 12A displays bodyweight changes in healthy canines following administration of EcCAR-MSCS as compared to control. No significant differences in body weight changes were found between groups. Data showing mean ± s.d. of % weight change from baseline with statistical analysis performed by ordinary 1-way ANOVA (ns = p ≥ 0.05). Figure 12B contains data displaying transverse colonic tissue sections of canines through H&E staining 28 days following administration at 20x and 40x magnification following treatment with human EcCAR-MSC (left) or control (right). Figure 13 is a histogram showing CAR expression on MSCs containing variable intracellular signaling domains including 4-1BB, CD28, TLR, and IFN? signaling domains as detected by flow cytometry using CAR ⁺ FMC63 antibody. Data shown are mean +/- s.d. representative of at > 6 independent experiment using 5 MSC donors. Figure 14 contains a schematic of exemplary mechanisms for enhancing immunosuppression and trafficking of CAR-MSCs. Figures 15A-15F show that MSCs are stably transduced to express CAR and maintain stem-like features following transduction and stimulation. Figure 15A is a representative flow cytometry plot depicting CAR19 expression following lentiviral transduction of MSCs with increasing concentrations of protamine sulfate enhancer (50 ug/mL and 100 ug/mL, as indicated) compared to untransduced (UTD) MSCs. Data are representative using 6 different biological MSC donors. Figure 15B is a histogram showing CAR expression of anti-Ecad CAR and anti-CD19 CAR positive control as detected by flow cytometry. Data shown are mean ± standard deviation (s.d.) of 6 different biological MSC donors. Figure 15C is a graph showing CAR expression on EcCAR-MSC compared to UTD-MSC by flow cytometry 2 days and 11 days following transduction and ex vivo expansion. Data shown are mean ± s.d. representative of 3 independent experiments using 3 MSC donors. Statistical analysis was performed by 2-way ANOVA (****p≤0.0001). Figure 15D is a histogram showing EcCAR expression on MSCs across 3 different primary biological MSC donors. Data are representative of ≥10 independent experiments using 6 different MSC donors. Figure 15E is a graph showing the stem phenotype of EcCAR-MSC and UTD-MSC measured with flow cytometry after staining MSCs for CD105, CD90, CD73, CD34, CD45, and CD14 surface markers. Data shown are mean ± s.d. results of 3 independent experiments of 4 biological MSC donors. Statistics were performed by 2-way ANOVA (ns=p≥0.05). Figure 15F depicts two graphs of bulk RNAseq analysis of upregulated (left panel) and downregulated (right panel) phenotypic enrichments of EcCAR-MSCs as compared to UTD-MSCs by CellMarker Augmented gene set enrichment analysis. Significant genes were selected by ≥1 or ≤-1 log fold change and ?0.05 adjusted p values (padj) via differential expression analysis of 3 individual MSC donors. Dashed line across x axes represent statistically significant enrichment for all pathways -log(p≤.05). Figures 16A-16G show that EcCAR-MSCs demonstrate superior antigen-specific suppression of primary T cells in vitro. Figure 16A is a histogram displaying establishment of Ecad ⁺ NALM6 with matched Ecad- NALM6, making the Ecad cell-based stimulation appropriate for use in in vitro suppression assays and in vivo tumor models. Figure 16B is a graph of the absolute numbers of CD3 ⁺ T cells following coculture with EcCAR-MSCs or UTD-MSCs with increasing concentrations of soluble Ecad (0ng/mL, 250ng/mL, and 1000ng/mL). Data shown are mean ± s.d. of 3 independent experiments using 3 individual MSC donors. Statistics were performed by 2-way ANOVA (***p≤ 0.001). Figure 16C is a graph of the stem phenotype of EcCAR MSC with increasing (0 250 or 1000 ng/mL) soluble Ecad stimulation measured with flow cytometry after staining MSCs for CD73, CD90, CD105, CD14, CD34, and CD45. Data shown are mean ± s.d. using 4 different MSC donors. Statistics were performed using a 2-way ANOVA (ns=p≥0.05). Figures 16D, 16E, and 16F are graphs of the absolute numbers of CD3 ⁺ T cells of MSCs from 3 different donors following co-culture with EcCAR-MSCs or UTD-MSCs derived with or without Ecad ⁺ or Ecad- cell-based stimulation. Data shown are mean ± s.d. Statistics were performed using a 2- way ANOVA (n=2-3 replicates per donor) (*p≤0.05, **p≤0.01). Figure 16G is a graph of the stem phenotype of EcCAR-MSCs or UTD-MSCs following co-culture alone or with Ecad ⁺ or Ecad- cell-based stimulation measured by flow cytometry after staining MSCs for CD73, CD90, CD105, CD14, CD34, and CD45. Data shown are mean ± s.d. results from n=3 MSC donors. Statistics were performed using a 2-way ANOVA (ns=p≥0.05). Figures 17A-17G show that EcCAR-MSCs induce superior immunosuppression in tumor and GvHD Xenograft models. Figure 17A is a schematic of an exemplary method for evaluating the effect of Ecad ⁺ in a Nalm6 xenograft tumor model. Immunocompromised NOD-SCID-? ^-/- (NSG) mice were engrafted with luciferase (luc) ⁺ Ecad ⁺ or luc ⁺ Ecad-NALM6 cells (1 x 10 ⁶ cells i.v.) and treated with CD19-targeted CAR T (CART19) (1 x 10 ⁶ cells i.v.). Mice were then randomized to receive untransduced MSCs (UTD-MSCs) or EcCAR-MSCs (1 x 10 ⁶ cells i.p.) and monitored for tumor burden by bioluminescent imaging (BLI) and monitored for survival and health. Figure 17B is a graph of Ecad ⁺ NALM6 tumor flux following CART19 infusion in the Nalm6 model, comparing UTD- MSCs and EcCAR-MSCs. Data shown are median ± standard error of the mean (SEM) with statistical analysis using a 2-way ANOVA (***p ≤ 0.001; n=4-5 mice per group, 2 independent experiments). Figure 17C is a graph of Ecad- NALM6 tumor flux following CART19 infusion in the Nalm6 model, comparing UTD-MSCs and EcCAR-MSCs. Data shown are median ± SEM with statistical analysis using a 2-way ANOVA (ns=p≥0.05; n=4-5 mice per group; 2 independent experiments). Figure 17D is a schematic of an exemplary method for evaluating the effect of EcCAR-MSCs in a human PBMC-induced GvHD xenograft model. Human peripheral blood mononuclear cells (PBMCs) were injected (25-30 x 10 ⁶ cells i.v) into NSG mice that had been randomized to receive treatment with EcCAR- MSCs or UTD MSCs (1 x 10 ⁶ cells ip) Mice were monitored for weight loss the development of clinical GvHD symptoms (scored based on weight loss, diarrhea, posture, activity, fur texture, and skin integrity), and survival. Figure 17E is a graph of the percent weight change from baseline in GvHD xenografts following treatment with UTD-MSCs, EcCAR-MSCs, or no treatment. Data shown are mean ± SEM with statistical analysis using a 2-way ANOVA (ns=p≥0.05, *p ≤ 0.05 ****p≤0.0001; n=5 mice per group, 3 independent experiments). Figure 17F is a graph of the GvHD clinical scoring severity (left) following treatment with EcCAR-MSCs, UTD-MSCs, or no MSCs, with representative mouse images (right). Data shown are mean ± SEM with statistical analysis using a 2-way ANOVA (ns=p≥0.05, *p ≤ 0.05 n=5 mice per group, 3 independent experiments). Figure 17G is a graph of the survival outcomes following treatment with EcCAR-MSCs compared to UTD- MSCs and no MSC control. Statistical analysis used a Kaplan-Meier survival analysis (ns=p≥0.05, *p≥0.05, **p≤0.01; n=5 mice per group). Figures 18A-18G shows that EcCAR-MSCs display antigen-specific activation and trafficking to Ecad ⁺ colonic target tissue in acute GvHD xenograft models. Figure 18A is a schematic of an exemplary method of for evaluating the effect of Ecad ⁺ in an acute GvHD xenograft model. Immunocompromised NOD-SCID-? ^-/- (NSG) mice were first irradiated at 250cGy to further prime an inflammatory environment. Human PBMCs were injected (10-15 x 10 ⁶ cells i.v) into mice along with luc ⁺ GFP ⁺ Ecad-CAR-MSCs or luc ⁺ GFP ⁺ CD19-CAR- MSCs (1 x 10 ⁶ cells i.p.). Mice were monitored for long-term weight loss, the development of clinical GvHD, and survival. Satellite mice were isolated one week following MSC injection for assessment of MSC localization in colonic target organs by bioluminescent imaging and immunofluorescent staining. Figure 18B is a graph of the percent weight change from baseline in acute GvHD xenografts following treatment with Ecad-CAR-MSCs, CD19- CAR-MSCs, or no treatment. Data shown are mean ± SEM with statistical analysis using a 2- way ANOVA (**p≤0.01, ***p ≤ 0.001; n=4-5 mice per group, 3 independent experiments). Figure 18C is a graph of survival outcomes following treatment with Ecad-CAR-MSCs compared to CD19-CAR-MSCs and no MSC control. Statistical analysis used a Kaplan- Meier survival analysis (*p ≤ 0.0;5 n=4-5 mice per group). Figure 18D is a graph of the absolute number of human CD3 ⁺ T cells in peripheral blood comparing Ecad-CAR-MSC and CD19 CAR MSC treated mice by flow cytometry 2 weeks following MSC injection Data shown are mean ± s.d. with statistical analysis using an ordinary 1-way ANOVA (*p ≤ 0.0;5 n=4-5 mice per group, 2 independent experiments). Figure 18E shows representative bioluminescent imaging across luc ⁺ CD19-CAR-MSC and Ecad-CAR-MSC treated mice (left) with percent MSC flux to colon relative to total flux detected across all organs (right). Data shown are mean +/- s.d. with statistical analysis using unpaired t-test (*p ≤ 0.0;5 n=4-5 mice per group, 2 independent experiments). Figure 18F is a graph of immunofluorescent- based quantification of EcCAR-MSC compared to CD19-CAR-MSC localization to Ecad ⁺ colon tissue. Data were determined by the percent of MSC ⁺ colonic crypts per focal image. Data shown are mean ± s.d. with statistical analysis using and ordinary 1-way ANOVA (**p?0.01; n=3 mice per group). Figure 18G is a series of representative immunofluorescent image of mouse colonic tissue isolated from acute GvHD xenograft models 7 days following GFP ⁺ MSC administration. Comparisons are between CD19-CAR-MSC and Ecad-CAR- MSC (2 ^nd row) colocalization with E-cadherin ⁺ (3 ^rd row) colonic regions. Cell nuclei are stained with DAPI with each color channel displayed to make merged image. Images obtained at 40x magnification capturing 1x crop area. Figures 19A-19F show that activation of antigen-specific immunosuppressive signaling pathways identified in EcCAR-MSCs. Figure 19A is a heat map depicting the distinct gene expression profile of stimulated EcCAR-MSC+Ecad samples highlighting the functional impact of CAR antigen-specific stimulation through hierarchical clustering with unstimulated EcCAR-MSC, stimulated UTD-MSC+Ecad, and unstimulated UTD-MSC samples. Data shown are gene fold counts normalized across all samples (padj?0.05)(n=3 MSC donors per condition). Figure 19B is a graph of a principal Component Analysis (PCA) of gene expression profiles across 6 samples cluster by derived MSC donor in stimulated compared to unstimulated UTD-MSCs. Figure 19C is a graph of a PCA of gene expression profiles of stimulated compared to unstimulated EcCAR-MSCs and reveals unique clustering by stimulation group. Figure 19D is a schematic summary of an analysis using Ingenuity Pathway Analysis (IPA) machine learning algorithm illustrating factors activated when stimulated EcCAR-MSCs compared to unstimulated EcCAR-MSCs. Factors including upstream regulators, canonical pathways, and biological functions were combined to predict meaningful functional impacts Analysis revealed that apoptosis of leukocytes (center) to be the most significantly enriched (padj<O.OOOl) functional pathway directly associated with all 17 activated molecules predicted in the dataset including CD28 CAR signaling molecule. Figure 19E is a graphical representation of the IPA of Figure 16D revealing upregulated canonical pathways in stimulated EcCAR-MSCs compared to unstimulated EcCAR-MSCs. Dashed line across x axes represent statistically significant enrichment for all pathways - log(p< 05) (n=3 MSC donors per group). Figure 19F is a series of graphs of normalized gene count comparisons across unstimulated UTD-MSCs, stimulated UTD-MSCs, unstimulated EcCAR-MSCs, and stimulated EcCAR-MSCs. CD28-linked transcription factor genes (NFKB I, JUN, RELB, and IRF1) and downstream effector genes (TRAF1, TLR3, FYN) in stimulated EcCAR-MSC group only. Data shown are mean ± s.d. Gene counts are normalized across groups. Statistical analysis used a 1-way ANOVA (ns=p>0.05, *p<0.05, **p≤0.01, ***p≤ 0.001, ****p≤0.0001).

Figures 20A-20H show that EcCAR-MSC stimulation resulted in increased cytokine secretion, surface marker expression, and subsequent T cell modulation. Figure 20A is a heatmap displaying upregulated cytokines in Ecad ⁺ cell line stimulation compared to Ecad' cell line stimulation on T cells alone, UTD-MSCs, and EcCAR-MSCs by multiplexed cytokine assay. Data shown are degree of cytokine fold-change as measured by multiplexed assay normalized by smallest (0) and largest (100) values per cytokine (n=2 technical replicates per assay). Figure 20B is a series of graphs of inhibitory surface marker expression across UTD-MSCs and EcCAR-MSCs with Ecad ⁺ cell line stimulation as compared to Ecad' cell line stimulation. Data shown are mean ± s.d. results with statistical analysis using a 2- way ANOVA 0.001, ****p≤0.0001; n= 3 replicates per donor). Figure 20C is a series of graphs of enriched serum cytokines (IL-10, TNFa, G-CSF, eotaxin, and FGF-2 by pg/mL) at 2 weeks in EcCAR-MSC-treated mice from tumor xenografts. Data shown are mean ± SEM with statistical analysis using an ordinary 1-way ANOVA (*p≤0.05, **p≤0.01, ***p≤ 0.001, ****p≤0.0001; n=4-6 mice per group). Figure 20D is a graph of the percent weight change compared to baseline showing prevention of GvHD-induced weight loss following single dose treatment of EcCAR-MSCs compared to UTD-MSCs. Displaying mean ± SEM of percent weight change. Statistical analysis used a 2-way ANOVA (***p≤ 0.001; n=5 mice per group). Figure 20E is a graph of the absolute number of human CD3 ⁺ T cells in mouse peripheral blood in EcCAR-MSC and UTD-MSC treatment groups as measured by flow cytometry 2 weeks following first MSC injection. Data shown are mean ± s.d. with statistical analysis using an unpaired t- test (**p≤0.01; n=5 mice per group). Figure 20F is a graph of human CD4 ⁺ and CD8 ⁺ T cells quantified in mouse peripheral blood 2 weeks following EcCAR-MSC treatment. Data shown are mean ± s.d. cell counts. Statistical analysis used a 2- way ANOVA (*p?0.05, ***p≤ 0.001; n=5 mice per group). Figure 20G is a graph showing an alteration in human CD4 ⁺ to CD8 ⁺ T cell proportions in mice treated with EcCAR-MSCs compared to treatment with UTD-MSCs. Data shown are mean ± s.d. of percent cell subsets. Statistical analysis used a 2-way ANOVA (**p≤0.01; n=5 mice per group). Figure 20H is a graph of human CD4 ⁺ CD25 ⁺ CD127- Treg cell subsets 4 weeks following MSC treatment in GvHD xenograft mice. Data shown are mean ± s.d. % of cells. Statistical analysis used an unpaired t-test (***p≤ 0.001; n=4 mice per group). Figures 21A-21G show that the CD28 signaling domain within EcCAR-MSCs increases immunosuppressive efficacy. Figure 21A is a schematic of an exemplary method of EcCAR-MSC construct designs used to investigate CAR-MSC mechanism of action. Constructs contained the full CD28ζ, CD28 alone, CD3 ζ alone, and null (no signaling domain) EcCAR-MSCs. Figure 21B is a histogram of CAR expression on MSCs for CD28ζ, CD28, CD3 ζ, and null EcCAR-MSC constructs detected by flow cytometry. Displaying CAR % expression representing ?5 independent experiments on 4 independent MSC donors. Figure 21C is a series of graphs showing the degree of CD3 ⁺ T cell suppression following Ecad ⁺ cell line stimulation across each EcCAR-MSC signaling domain subtype or T cells alone in culture with Ecad ⁺ and matched Ecad- cell line. Data shown are mean ± s.d. representative of 4 primary T cell donors. Statistical analysis used a 1-way ANOVA (ns=p≥0.05, *p≤0.05, **p≤0.01, ***p≤ 0.001; n=3 technical replicates per donor). Figure 21D is a schematic of a representative method to test the effect of various CAR-MSC signaling domains in an acute GvHD xenograft mouse model. NSG mice were irradiated at 250cGy to prime inflammatory environment. Human PBMCs were injected (10-15 x 10 ⁶ cells i.v) into mice along with one of the following MSC groups: CD28ζ, CD28, CD3 ζ, or null EcCAR-MSCs, UTD-MSCs (1 x 10 ⁶ cells i.p.), or “No MSC” treatment. Mice were monitored for long-term weight loss, the development of clinical GvHD symptoms, and survival. Figure 21E is a graph of the percent weight change from baseline in the acute GvHD xenografts following treatment with each of the MSC groups or no treatment. Data shown are mean ± SEM with statistical analysis using a 2-way ANOVA (ns=p≥0.05, *p ≤ 0.0,5 **p≤0.01; n=5-6 mice per group, 2 independent experiments). Figure 21F is a graph of the GvHD clinical scoring severity of symptom progression following treatment with alternative MSC signaling domains. Data shown are mean ± SEM with statistical analysis using a 2-way ANOVA (*p ≤ 0.0;5 n=5-6 mice per group, 2 independent experiments). Figure 21G is a graph of the survival outcomes of acute GvHD xenograft mouse model mice following treatment with each EcCAR-MSC subtype. Data depicting trends in enhanced survival, but without statistical significance, are included with prospective p value measurements. Statistical analysis used a Kaplan-Meier survival analysis (ns=p≥0.05, *p ≤ 0.0,5 **p≤0.01; n=5-6 mice per group). Figures 22A-22I show EcCAR-MSC safety and clearance profiles across tissues. Figure 22A is a schematic for a representative method to determine the effect of EcCAR- MSCs in a MSC persistence model. Either luc ⁺ GFP ⁺ UTD-MSCs or luc ⁺ GFP ⁺ CAR-MSCs were injected into human PBMC-primed NSG mice with or without CAR stimulation through coadministration of irradiated Ecad ⁺ cells. Mice were followed by serial biweekly bioluminescent imaging (BLI). Figure 22B is a representative image of luciferase ⁺ MSC expansion and clearance in mice from 3 to 24 days following administration. Figure 22C is a graph of the MSC expansion and clearance kinetics following administration of EcCAR- MSCs or UTD-MSCs with or without additional Ecad stimulation as measured by flux of BLI. Data shown are mean BLI with statistical analysis using a 2-way ANOVA (ns=p≥0.05; n=4-5 mice per group). Figure 22D is a graph of the absolute number of keratinocytes following 24-hour coculture with UTD-MSCs or EcCAR-MSCs. Data shown are mean ± s.d. with statistical analysis using a paired t-test (ns=p≥0.05; n= 3 replicates per donor). Figure 22E is a graph of Ecad expression identified on keratinocytes following 24-hour coculture with UTD-MSCs or EcCAR-MSCs. Data shown are mean % ± s.d. with statistical analysis using a paired t-test (ns=p≥0.05; n= 3 replicates per donor). Figure 22F is a heatmap displaying upregulated cytokines across UTD-MSCS, EcCAR-MSCs, and keratinocytes at baseline and following 24 hour coculture conditions Data shown are cytokine levels measured by multiplexed assay normalized by smallest (0) and largest (100) values per cytokine (n=2 technical replicates per assay). Figure 22G is a graph of the absolute number of bronchial cells following 24-hour coculture with varying ratios of UTD-MSCs or EcCAR- MSCs. Shown data are mean ± s.d. with statistical analysis using a paired t-test (ns=p≥0.05; n= 3 technical replicates). Figure 22H is a graph of immunofluorescent-based quantification of EcCAR-MSC localization compared to CD19-CAR-MSC localization in Ecad ⁺ lung tissue. Data was determined by the % of MSC ⁺ regions per focal image. Data shown are mean ± s.d. with statistical analysis using an ordinary 1-way ANOVA (ns=p≥0.05; n=3 mice per group). Figure 22I is a representative image of immunofluorescence imaging of mouse bronchial (lung) tissue isolated from acute GvHD xenograft model 7 days following GFP ⁺ MSC administration. Comparisons are between colocalization of Ecad ⁺ (2 ^nd column) to bronchial regions in CD19-CAR-MSC and Ecad-CAR-MSC (last column) treated mice. Cell nuclei are stained with DAPI (3 ^rd column) with each color channel displayed to make merged image. Images obtained at 40x magnification capturing 1x crop area. Figures 23A-23D show EcCAR construct design and manufacturing. Figure 23A is a representative sequence of an optimized anti-Ecad scFv clone sequence (hmcECAD.6) identified through phage display generation with Ecad selection. hmcECAD was selected with affinity to human, mouse, and canine cross-reactivity and cloned into EcCAR construct to generate EcCAR-MSCs. Figure 23B is a representative schematic of a full EcCAR-MSC construct containing hmcCAD heavy and light chains for binding to Ecad, CD28 hinge and transmembrane domains for passage through MSC cell membrane, and CD28 intracellular signaling domain for immunosuppressive activation with CD3 ζ costimulation as regularly employed for CAR construct stability. Figure 23C is a graph of phage ELISA results used to test the relative affinity of hmcECAD.6 scFv clone to mouse Ecad as compared to FLAG tag positive control. Data shown are all technical replicates (n=3) with statistical analysis using a 2-way ANOVA (ns=p≥0.05). Figure 23D is a graph showing dose-dependent killing of human and mouse Ecad ⁺ tumors (MCF7 and 4T1, respectively) by CART cells containing hmcECAD.6 scFv construct. Data shown are all technical replicates (n=3) with statistical analysis using a 2-way ANOVA (**p≤0.01, ****p≤0.0001). Figures 24A-24D show an exemplary method and confirmation of the generation of CAR-MSCS with verification of sternness. Figure 24A is a schematic of an exemplary method for EcCAR-MSC generation in culture following thawing from cryogenic storage systems. Briefly, following in vitro outgrowth in T 175 flasks, MSCs are digested and quantified for transduction with optimized CAR plasmid-containing lentiviral vector delivery system and protamine sulfate enhancer. CAR % confirmation is completed by day 5 via flow cytometric analysis of goat anti-mouse antibody. Figure 24B is a graph of the stem phenotype of EcCAR-MSC with and without Ecad ⁺ cell line stimulation measured by flow cytometry after staining with surface markers and with additional positive control measurements using primary naive T cells. Data shown are mean ± s.d. from 3 individual MSC donors. Statistical analysis used a 2-way ANOVA (****p≤0.0001). Figure 24C is a representative image of UTD-MSC and CAR-MSC morphological comparisons at baseline and with the addition of matched Ecad" and Ecad ⁺ cell line as a means of CAR antigenspecific stimulation. Figure 24D is series of histograms characterizing MSC stem phenotype by positive CD105, CD90, and CD73 and negative CD34, CD45, and CD14 surface markers. Positive gates were established by the fluorescence minus one (FMO) method for negative control (top) for positive sample quantification of UTD-MSCs (middle) and EcCAR-MSCs (bottom).

Figures 25A-25G show the effect of EcCAR-MSCs on CART effector functions in in vivo tumor model. Figure 25A is a graph comparing of Ecad'NALM6 and Ecad ⁺ NALM6 tumor flux measurements across control mice without CART 19 cell infusion. Data shown are mean ± SEM with statistical analysis using a 2-way ANOVA (ns=p≥0.05; n=4-5 mice per group). Figures 25B and 25C are graphs of the relative levels of luc ⁺ Ecad'NALM6 (Figure 25B) and luc ⁺ Ecad ⁺ NALM6 (Figure 25C) as measured by luminescence following 24-hour in vitro coculture with UTD-MSCs or EcCAR-MSCs at varying MSC to NALM6 ratios. Data shown are mean ± s.d. with statistical analysis using a 2-way ANOVA (ns=p>0.05; n=2 replicates per group). Figure 25D is a representative schematic of a method of evaluating CART 19 in NALM6 and JeKo-1 tumor models. NSG mice engrafted with luciferase ⁺ CD19 ⁺ Nahn6 or JeKo-1 cells (1 x 10 ⁶ i.v.) and treated with CART 19 (1 x 10 ⁶ cells i.v.) and irradiated Ecad ⁺ cell line. Mice were then randomized to receive UTD-MSCs or EcCAR- MSCs (1 x 10 ⁶ cells i.p.) and monitored biweekly for bioluminescent imaging and survival. Figure 25E is a graph of tumor flux following CART 19 infusion in Jeko-1 tumor model, comparing EcCAR-MSCs, UTD-MSCs, or no MSC treatment. Data shown are mean ± SEM with statistical analysis by 2-way ANOVA (**p≤0.01; n=3-4 mice per group). Figure 25F is a graph of tumor flux measurements across MSC administration groups following CART 19 infusion in NALM6 model. Data shown are mean ± SEM with statistical analysis using a 2- way ANOVA (ns=p>0.05, ***p ≤ 0.001; n=3-4 mice per group, 2 independent experiments). Figure 25g is a graph of the survival outcomes of mice following treatment with EcCAR- MSCs compared to UTD-MSCs and no MSC control groups. Statistical analysis use a Kaplan-Meier survival analysis (ns=p≥0.05, *p≤0.05; n=3-4 mice per group, 2 independent experiments).

Figures 26A-26B show exemplary flow cytometry gating strategies. Figure 26A is an exemplary gating strategy used for identification of positive MSC surface markers as verified by FMO and internal controls. MSC populations are identified by size, single cells are selected through diagonal gating, live MSCs are stained with live/dead fixable aqua fluorophore to exclude dead cells, and positive cell markers (CAR ⁺ % shown) are identified based on positive gating (verified by internal and FMO controls) of cellular stain of interest. Figure 26B is an exemplary gating strategy used for identification of luciferase ⁺ and CAR ⁺ MSCs for assessment in in vivo clearance experiments. MSCs were transduced with both luciferase-expressing transgene as well as CAR construct and compared to luciferase ⁺ MSC and UTD-MSC controls. Results indicate successful transduction of luciferase and CAR with >50% double luciferase* CAR* for intraperitoneal injection in vivo.

Figures 27A-27E show bulk RNAseq pathway analysis and cytokine secretion. Figure 27A is a graph showing a summary of differentially expressed genes in unstimulated EcCAR-MSCs compared to UTD-MSCs, Ecad-stimulated compared to unstimulated EcCAR-MSCs, Ecad-stimulated compared to unstimulated UTD-MSCs, and Ecad-stimulated EcCAR-MSCs compared to UTD-MSCs. Data shown are gene counts of significantly unregulated and downregulated genes within comparisons with adj. p value <0.01 and ± 1- log fold change. Transcriptional alterations induced by Ecad stimulation of CAR-MSCs included 2362 significant genes compared to EcCAR-MSC alone and 3032 significant genes compared to Ecad stimulated UTD-MSCs. Transcriptional alterations induced by CAR transduction included 606 significant genes. Transcriptional alterations induced by Ecad stimulation included 206 significant genes. Figure 27B is a graph of an Ingenuity Pathway Analysis (IPA) revealing upregulated canonical pathways in unstimulated EcCAR-MSCs compared to UTD-MSCs. Dashed line across x axes represent statistically significant enrichment for all pathways -log(p?.05) (n=3 MSC donors per group). Figure 27C and 27D are graphical summaries of the IPA of Figure 27B illustrating significant entities activated in unstimulated EcCAR-MSCs vs. UTD-MSCs (Figure 27C) and significant entities activated in stimulated EcCAR-MSCs compared to UTD-MSCs (Figure 27D). Canonical pathways and activated molecules were used to predict meaningful functional impacts between datasets. Figure 27E is a graph showing serum cytokine elevations found in peripheral blood from EcCAR-MSC-treated tumor xenograft mice as compared to UTD-MSC and control. Cytokines include macrophage-derived chemokine (MDC), growth related alpha protein (GRO), granulocyte macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 3 (MCP-3), and FMS-related tyrosine kinase 3 ligand (Flt-3L) in pg/mL. Data showing mean ± s.d. with statistical analysis determined by multiple t tests (*p ≤ 0.05, **p ≤0.01, ****p ≤ 0.0001; n= 4-6 mice per group). Figures 28A-28E show EcCAR-MSC safety profiles as determined using an in vivo canine model. Figure 28A is a schematic for an exemplary method of CAR-MSC manufacturing and safety analysis in a healthy canine model. EcCARs with cross reactivity to human, mouse, and canine Ecad were lentivirally transduced into human MSCs and expanded in vitro for subsequent i.p. injection into healthy canine subjects. Subgroups were monitored for hematological and organ toxicity for 28 days. Figure 28B is a series of graph of the complete blood count levels displayed as a determinant of hematopoietic safety following administration of EcCAR-MSCs. This includes white blood cells, monocytes, lymphocytes, neutrophils, and platelets with short term (3 day) and long term (28 day) blood level monitoring following in vivo EcCAR-MSC injection as compared to baseline. Displaying mean ± s.d. of blood composition with statistics by 1-way ANOVA (ns=p≥0.05; n=3 subjects per experimental group). Figure 28C is a series of graphs of total protein, BUN, creatinine albumin and alkaline phosphatase levels depicted for safety confirmation with short term (3 day) and long term (28 day) monitoring following in vivo EcCAR-MSC injection. Data shown are mean ± s.d. with statistical analysis using a 1-way ANOVA (ns=p≥0.05; n=3 subjects per experimental group). Figure 28D is a graph of bodyweight changes in healthy canines following administration of EcCAR-MSCS as compared to control. No significant differences in body weight changes were found between groups. Data shown are mean ± s.d. of % weight change from baseline with statistical analysis performed by ordinary 1-way ANOVA (ns=p≥0.05), (ns=p≥0.05; n=3 subjects per experimental group). Figure 28E is a representative image of transverse colonic tissue sections of canines through H&E staining 28 days following administration at 20x and 40x magnification following treatment with human EcCAR-MSCs (left) or control (right). Figure 29 is a graph depicting the percentage of EcCAR positivity following transduction of mouse adipose-derived MSCs as determined by flow cytometry. Data shown are mean +/- s.d. representative of 3 technical mouse cell line replicates. D ^{ETAILED DESCRIPTION} This document provides methods and materials involved in treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD). In some cases, one or more CAR-MSCs having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can be administered to a mammal to induce an immunosuppressive response (e.g., to reduce or eliminate an inflammatory immune response) in a targeted tissue within the mammal. For example, a CAR-MSC can express a CAR that can target an epithelial-specific antigen (e.g., Ecad), also referred to as CDH1)) to target the MSC to epithelial tissues, and also can have (e.g., can be engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to enhance immunosuppression within the targeted epithelial tissues. In some cases, a CAR-MSC can express a CAR that can target a neural-specific antigen (e.g., myelin oligodendrocyte glycoprotein (MOG)) to target the MSC to neural tissues and also can have (e.g., can be engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to enhance immunosuppression within the targeted neural tissues. For example, one or more CAR-MSCs having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can be administered (e.g., by adoptive transfer) to a mammal (e.g., a human) having (or at risk of developing) an inflammatory disease or condition to treat one or more autoimmune diseases (e.g., GVHD) in a targeted tissue (e.g., an inflamed tissue) within the mammal. The term “elevated level” as used herein with respect to a level of a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) refers to any level that is higher than a reference level of that polypeptide. The term “reference level” as used herein with respect to a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) refers to the level of that polypeptide typically observed in a MSC (e.g., a CAR- MSC) not engineered to have an elevated level of that polypeptide as described herein. A MSC described herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be any appropriate MSC. Examples of MSCs that can be used as described herein include, without limitation, MSCs derived from adipose, MSCs derived from bone marrow, MSCs derived from placental tissue, MSCs derived from dental pulp tissue, MSCs derived from an umbilical cord, MSCs derived from cord blood, MSCs derived from Wharton’s jelly, MSCs derived from dermis, MSCs derived from olfactory mucosa, MSCs derived from peripheral blood, and MSCs derived from an amniotic membrane. For example, a CAR-MSC having (e.g., engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can be an adipose derived-MSC. A CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can express any appropriate CAR. A CAR can include (a) an antigen-binding domain, (b) a transmembrane domain, and (c) one or more signaling domains. An antigen-binding domain of a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be any appropriate antigen-binding domain. In some cases, an antigen-binding domain can include an antibody or a fragment thereof that targets an antigen (e.g., a tissue-specific antigen such as an epithelial-specific antigen or a neural- specific antigen). Examples of antigen-binding domains include, without limitation, an antigen-binding fragment (Fab), a variable region of an antibody heavy (VH) chain, a variable region of a light (VL) chain, and a single chain variable fragment (scFv). In some cases, an antigen-binding domain can target (e.g., can target and bind to) a tissue-specific antigen (e.g., an epithelial-specific antigen or a neural-specific antigen). For example, a CAR-MSC described herein can express (e.g., can be engineered to express) a CAR that can bind to a tissue-specific antigen (e.g., an antigen present on cells within a tissue with minimal, or no, expression on other cell types). In some cases, a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be engineered to express a CAR that can target (e.g., can target and bind to) an antigen (e.g., a cell surface antigen) expressed by epithelial cells (e.g., an epithelial-specific antigen or an epithelial antigen) in a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) within an epithelial tissue. An epithelial-specific antigen can be any appropriate epithelial-specific antigen. An epithelial-specific antigen can be expressed on any appropriate type of epithelial cell (e.g., gastrointestinal tract cells such as colon cells and rectal cells, skin cells, lung cells, liver cells, genital tract cells, and urinary tract cells). In some cases, an epithelial-specific antigen can be a cell adhesion molecule (CAM). In some cases, an epithelial-specific antigen can be an integrin (eg a gut integrin) Examples of epithelial specific antigens include without limitation, Ecad, CD 103, αEβ7, and α4β7. For example, a CAR-MSC engineered to target epithelial tissues can bind to Ecad. In some cases, a CAR-MSC can be engineered to express a CAR-Ecad to target Ecad expressed by epithelial cells in a mammal. In some cases, a CAR expressed by a CAR-MSC provided herein can include an Ecad binding domain. For example, a CAR expressed by a CAR-MSC provided herein can include an anti-Ecad scFv that includes a heavy chain comprising the CDRs set forth in SEQ ID NO: 1, and a light chain comprising the CDRs set forth in SEQ ID NO:2. For example, a CAR expressed by a CAR- MSC provided herein can have an anti-Ecad scFv that includes a heavy chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:1 and includes a light chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:2 (see, e.g., Example 2). In some cases, a CAR expressed by a CAR-MSC provided herein can include a CD 103 binding domain. For example, a CAR expressed by a CAR-MSC provided herein can include an anti-CD103 scFv that includes a heavy chain comprising the CDRs set forth in SEQ ID NO: 3, and a light chain comprising the CDRs set forth in SEQ ID NO:4. For example, a CAR expressed by a CAR-MSC provided herein can have an anti-CD103 scFv that includes a heavy chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO: 3 and includes a light chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:4 (see, e.g., Example 2).

In some cases, a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be engineered to express a CAR that can target (e.g., can target and bind to) an antigen (e.g., a cell surface antigen) expressed by neural cells (e.g., a neural-specific antigen or a neural antigen) in a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as multiple sclerosis) within a neural tissue. When an antigen is a neural-specific antigen, the neural- specific antigen can be any appropriate neural-specific antigen. A neural- specific antigen can be expressed on any appropriate type of neural cell (e.g., sensory neurons, motor neurons, interneurons, glial cells, and neural sheath cells). A neural-specific antigen can be expressed on a neural cell in the central nervous system (CNS) and/or in the peripheral nervous system (PNS). In some cases, a neural-specific antigen can be a transmembrane protein. In some cases, a neural-specific antigen can target the myelin. Examples of neural-specific antigens include, without limitation, MOG and AMPA (e.g., an antigen on one or more AMPA receptor polypeptides). For example, a CAR-MSC engineered to target neural tissues can bind to MOG. In some cases, a CAR-MSC can be engineered to express a CAR-MOG to target MOG expressed by neural cells in a mammal having, or at risk of developing, multiple sclerosis. In some cases, a CAR expressed by a CAR-MSC provided herein can include a MOG antigen-binding domain. For example, a CAR expressed by a CAR-MSC provided herein can include an anti- MOG scFv that includes a heavy chain comprising the CDRs set forth in SEQ ID NO:5, and a light chain comprising the CDRs set forth in SEQ ID NO:6. For example, a CAR expressed by a CAR-MSC provided herein can have an anti-MOG scFv that includes a heavy chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:5 and includes a light chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:6 (see, e.g., Example 2). In some cases, a CAR expressed by a CAR-MSC provided herein can include an AMPA antigen-binding domain. For example, a CAR expressed by a CAR-MSC provided herein can include an anti-AMPA scFv that includes a heavy chain comprising the CDRs set forth in SEQ ID NO:7, and a light chain comprising the CDRs set forth in SEQ ID NO:8. For example, a CAR expressed by a CAR-MSC provided herein can have an anti-AMPA scFv that includes a heavy chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:7 and includes a light chain that comprises, consists essentially of, or consists of an amino acid sequence set forth in SEQ ID NO:8 (see, e.g., Example 2). A transmembrane domain of a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be any appropriate transmembrane domain. Examples of transmembrane domains that can be used as described herein include, without limitation, NKG2D transmembrane domains, CD8? transmembrane domains, CD28 transmembrane domains IgG4 transmembrane domains TNFR transmembrane domains and TLR transmembrane domains. In some cases, a transmembrane domain that is included in a CAR expressed by a CAR-MSC provided herein can be linked (e.g., covalently linked) to an adaptor polypeptide. In some cases, a CAR expressed by a CAR-MSC provided herein can include a CD28 transmembrane domain. For example, a CAR expressed by a CAR-MSC provided herein can include a CD28 transmembrane domain that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9 (see, e.g., Example 2). A signaling domain of a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can include any appropriate one or more signaling domains. For example, a CAR expressed by a CAR-MSC provided herein can be designed to include one, two, three, or four signaling domains. When a CAR expressed by a CAR-MSC provided herein provided herein includes more than one (e.g., two, three, or four) signaling domains, the CAR can include any appropriate combination of signaling domains. In some cases, a CAR expressed by a CAR-MSC provided herein can be designed to include one or more signaling domains normally found within an immune cell (e.g., a lymphocyte such as a TIL, a T cell, or a NK cell). In some cases, a CAR expressed by a CAR-MSC provided herein can be designed to include one or more signaling domains normally found within an MSC (e.g., an MSC with an immunosuppressive phenotype). In some cases, a CAR expressed by a CAR-MSC provided herein can be designed to include one or more regenerative signaling domains (e.g., to stimulate tissue regeneration). Examples of signaling domains that can be used as described herein include, without limitation, CD3zeta signaling domains, CD28 signaling domains, 4-1BB signaling domains, OX40 signaling domains, TLR3 signaling domains, TLR4 signaling domains, TIR3 signaling domains, TIR4 signaling domains, IFN? signaling domains, brain derived neurotrophic factor (BDNF) signaling domains, vascular endothelial derived growth factor receptor (VEGFR2) signaling domains, TLR3/TIR3 signaling domains, TLR4/TIR4 signaling domains, TLR9/TIR9 signaling domains, IFNGR1 signaling domains, IL10RA signaling domains, and TNFR2 signaling domains. In some cases a CAR expressed by a CAR MSC provided herein can be designed to be a first generation CAR having a CD3 ζ signaling domain. In some cases, a CAR expressed by a CAR-MSC provided herein can be designed to be a second generation CAR having a CD28 signaling domain followed by a CD3 ζ signaling domain. In some cases, a CAR expressed by a CAR-MSC provided herein can be designed to be a third generation CAR having (a) a CD28 signaling domain followed by (b) a CD27 signaling domain, an OX40 signaling domains, or a 4-1BB signaling domain followed by (c) a CD3 ζ signaling domain. In some cases, a CAR expressed by a CAR-MSC provided herein can include a CD28 signaling domain. For example, a CAR expressed by a CAR-MSC provided herein can include a CD28 signaling domain that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10 (see, e.g., Example 2) and a CD3 ζ signaling domain that comprises, consists essentially of, or consists of the amino acid set forth in SEQ ID NO:11 (see, e.g., Example 2). In some cases, a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can include one or more additional components. Examples of additional components that can be included in a CAR expressed by a CAR-MSC provided herein include, without limitation, linkers, hinge domains, and detectable markers. When an antigen receptor (e.g., a CAR) provided herein includes a detectable marker, the detectable marker can be any appropriate detectable marker. Examples of detectable markers that can be included in a CAR expressed by a CAR-MSC provided herein include, without limitation, bioluminescent polypeptides (e.g., luciferase polypeptides), fluorescent polypeptides (e.g., green fluorescent polypeptides (GFPs)), sodium iodine symporter (NIS), SSTR2 polypeptides, PSMA polypeptides, hdCK polypeptides, and eDHFR polypeptides. In some cases, a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can include an anti-Ecad scFv, a CD28 transmembrane domain, a CD28 signaling domain, and a CD3 ζ signaling domain. For example, a CAR expressed by a CAR- MSC provided herein can include an anti Ecad scFv having a heavy chain comprising the CDRs set forth in SEQ ID NO:1, and a light chain comprising the CDRs set forth in SEQ ID NO:2 (see, e.g., Example 2), a CD28 transmembrane domain that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:9 (see, e.g., Example 2), a CD28 signaling domain that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:10 (see, e.g., Example 2), and a CD3 ζ signaling domain that comprises, consists essentially of, or consists of the amino acid sequence set forth in SEQ ID NO:11 (see, e.g., Example 2). Any appropriate method can be used to express a CAR described herein (e.g., a CAR targeting a tissue-specific antigen such as an epithelial-specific antigen or a neural-specific antigen) on the surface of a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides). For example, a nucleic acid encoding a CAR can be introduced into a MSC. In some cases, a nucleic acid encoding a CAR can be introduced into a MSC by transduction (e.g., viral transduction) or transfection. In some cases, a nucleic acid encoding a CAR described herein can be introduced ex vivo into one or more MSCs. For example, ex vivo engineering of MSCs to express a CAR described herein can include transducing isolated MSCs with a vector (e.g., viral vector such as a lentiviral vector, a retroviral vector, an adenoviral vector, or an adeno-associated viral (AAV) vector) encoding a CAR. In cases where MSCs are engineered ex vivo to express a CAR, the MSCs can be obtained from any appropriate source (e.g., a mammal such as the mammal to be treated or a donor mammal, or a cell line). In some cases, CAR-MSCs can be prepared as described herein (see, e.g., Figure 7 and Example 1). For example, a CAR-Ecad can be expressed on a MSC to direct the MSC to epithelial tissues by introducing one or more constructs containing a nucleic acid encoding the CAR (e.g., a CAR targeting Ecad) into the MSC. For example, a CAR-MOG can be expressed on a MSC to direct the MSC to neural tissues by introducing one or more constructs containing a nucleic acid encoding the CAR (e.g., a CAR targeting MOG) into the MSC. In some cases, a CAR expressed by a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be a CAR as described elsewhere. See, for example, International Patent Application Publication No. WO 2021/092577 at, for example, page 18, line 16 to page 20, line 25, and page 21, line 29 to page 25, line 11. A CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or one and elevated level of one or more trafficking polypeptides) can express any appropriate one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides. In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be an exogenous polypeptide. In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be part of a signaling pathway (e.g., a TNFα signaling pathway, a TLR signaling pathway, and an IL-10 signaling pathway). In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be associated with T cell suppression. In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be a kinase (e.g., a tyrosine kinase). In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be a transcription factor. In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be chemokine (e.g., a homing chemokine). In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be a cytokine (e.g., an anti-inflammatory cytokine). In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be an immunomodulatory cell surface polypeptide. In some cases, a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) expressed by a CAR-MSC provided herein can be involved in cellular migration (e.g., transendothelial migration). Examples of immunosuppressive polypeptides and trafficking polypeptides that a CAR MSC provided herein can express (e.g., can be designed to express) include, without limitation, NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, CXCR4 polypeptides, CTLA4 polypeptides, TLR3 polypeptides, TLR4 polypeptides, TLR9 polypeptides, and TNFR2 polypeptides. Any appropriate method can be used to increase a level of one or more immunosuppressive polypeptides, to increase a level of one or more regenerative polypeptides, and/or to increase a level of one or more trafficking polypeptides in a CAR- MSC provided herein. In some cases, a nucleic acid (e.g., a n exogenous nucleic acid) encoding a polypeptide (e.g., an immunosuppressive polypeptide or a trafficking polypeptide) can be introduced into a CAR-MSC. For example, an exogenous nucleic acid encoding one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or one or more trafficking polypeptides can be introduced into a MSC by transduction (e.g., viral transduction) or transfection. In some cases, a nucleic acid (e.g., an endogenous nucleic acid) encoding one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or one or more trafficking polypeptides within a CAR- MSC can be modified to increase a level of expression of one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or one or more trafficking polypeptides in the CAR-MSC. For example, an endogenous nucleic acid encoding an immunosuppressive polypeptide, a regenerative polypeptide, or a trafficking polypeptide within a MSC can be modified by gene-editing techniques (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nucleases (Cas) systems, transcription activator-like effector nucleases (TALENs) systems, zinc finger nuclease (ZFN) systems, and base pair editing) to increase the level of expression of one or more immunosuppressive polypeptides, to increase a level of expression of one or more regenerative polypeptides, and/or to increase the level of one or more trafficking polypeptides in the CAR-MSC. In some cases, a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be engineered to have an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides ex vivo. For example, ex vivo engineering of CAR-MSCs to have an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can include transducing isolated CAR-MSCs with a vector (e.g., viral vector such as a lentiviral vector, a retroviral vector, an adenoviral vector, or an AAV vector) encoding the polypeptide(s). For example, ex vivo engineering of CAR-MSCs to have an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides can include transducing isolated CAR-MSCs with one or more lentiviral vectors encoding gene-editing components. Examples of NFkB1 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the National Center for Biotechnology Information (NCBI) databases at, for example, accession no. NM_001165412 (version NM_001165412.1), accession no. NM_001319226 (version NM_001319226.2), and accession no. NM_001382625 (version NM_001382625.1). In some cases, a NFkB1 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:12 (see, e.g., Example 2). Examples of JUN polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_002228 (version NM_002228.4), accession no. AL136985 (version AL13698511) and accession no CH471059 (version CH4710592) In some cases a JUN polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:13 (see, e.g., Example 2). Examples of RELB polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, NM_001411087 (version NM_001411087.1) and accession no. NM_006509 (version NM_006509.4). In some cases, a RELB polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:14 (see, e.g., Example 2). Examples of IRF1 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001354924 (version NM_001354924.1), accession no. NM_001354925 (version NM_001354925.1), and accession no. NM_002198 (version NM_002198.3). In some cases, a IRF1 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:15 (see, e.g., Example 2). Examples of TNFα polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_000594 (version NM_000594.4). In some cases, a TNFα polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:16 (see, e.g., Example 2). Examples of IL-10 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no NM 000572 (version NM 0005723) and accession no NM 001382624 (version NM_001382624.1). In some cases, a IL-10 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:17 (see, e.g., Example 2). Examples of FGF-2 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001361665 (version NM_001361665.2) and accession no. NM_002006 (version NM_002006.6). In some cases, a FGF-2 polypeptide that can be elevated in a CAR- MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:18 (see, e.g., Example 2). Examples of G-CSF polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_000759 (version NM_000759.4), accession no. NM_001178147 (version NM_001178147.2), and accession no. NM_172219 (version NM_172219.3). In some cases, a G-CSF polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:19 (see, e.g., Example 2). Examples of GM-CSF polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_000758 (version NM_000758.4), accession no. AC003959 (version AC003959.1), and accession no. DQ789232 (version DQ789232.1). In some cases, a GM-CSF polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:20 (see, e.g., Example 2). Examples of eotaxin polypeptides that can be elevated in a CAR-MSC provided herein (eg a CAR MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_002986 (version NM_002986.3), accession no. AC003959 (version AC003959.1), and accession no. CH471062 (version CH471062.2). In some cases, an eotaxin polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:21 (see, e.g., Example 2). Examples of Gal-9 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001330163 (version NM_001330163.2), accession no. NM_002308 (version NM_002308.4), and accession no. NM_009587 (version NM_009587.3). In some cases, a Gal-9 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:22 (see, e.g., Example 2). Examples of PD-1 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_005018 (version NM_005018.3), accession no. AF363458 (version AF363458.1), and accession no. EF064716 (version EF064716.1). In some cases, a PD-1 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:23 (see, e.g., Example 2). Examples of TIM-3 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_032782 (version NM_032782.5), accession no. CQ834184 (version CQ834184.1), and accession no. AC011377 (version AC011377.6). In some cases, a TIM-3 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:24 (see e g Example 2) Examples of CXCR3 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001142797 (version NM_001142797.2), accession no. NM_001504 (version NM_001504.2), and accession no. AB032738 (version AB032738.1). In some cases, a CXCR3 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:25 (see, e.g., Example 2). Examples of CXCR4 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001008540 (version NM_001008540.2), accession no. NM_001348056 (version NM_001348056.2), and accession no. NM_001348059 (version NM_001348059.2). In some cases, a CXCR4 polypeptide that can be elevated in a CAR- MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:26 (see, e.g., Example 2). Examples of CTLA4 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001037631 (version NM_001037631.2), NM_001037631 (version NM_001037631.3), and NM_005214 (version NM_005214.4 and NM_005214.5). In some cases, a CTLA4 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:91 (see, e.g., Example 2). Examples of TLR3 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no NM 003265 (version NM 0032652 and NM 0032653) NM 133484 ( NM_133484.2), and NM_126166 (version NM_126166.4). In some cases, a TLR3 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:92 (see, e.g., Example 2). Examples of TLR4 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_003266 (version NM_003266.4), NM_138557 (version NM_138557.3) and NM_138554 (version NM_138554.4). In some cases, a TLR4 polypeptide that can be elevated in a CAR-MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:93 (see, e.g., Example 2). Examples of TLR9 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_017442 (version NM_017442.3 and NM_017442.4) and NM_031178 (version NM_031178.2). In some cases, a TLR9 polypeptide that can be elevated in a CAR- MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:94 (see, e.g., Example 2). Examples of TNFR2 polypeptides that can be elevated in a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) include those set forth in the NCBI databases at, for example, accession no. NM_001066 (version NM_001066.2) and NM_011610 (version NM_011610.3). In some cases, a TNFR2 polypeptide that can be elevated in a CAR- MSC provided herein can have an amino acid sequence set forth in SEQ ID NO:95 (see, e.g., Example 2). This document also provides materials and methods for treating mammals in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) In some cases a mammal (eg a human) in need of immunosuppression can have (or be at risk of developing) GVHD. For example, one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be administered (e.g., by adoptive transfer) to a mammal having one or more autoimmune diseases to reduce the severity of the immune response within the mammal. Any appropriate method can be used to identify a mammal as being in need of immunosuppression. Once identified as being in need of immunosuppression, one or more CAR-MSCs provided herein can be administered to the mammal (e.g., a human) as described herein to reduce the immune response within the mammal by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, when treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein, the treatment can be effective to reduce inflammation within the mammal (e.g., within a targeted tissue within the mammal). For example, the methods and materials described herein can be used to reduce inflammation within a mammal having one or more autoimmune disorder (e.g., GVHD) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, when treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein, the treatment can be effective to increase the number of regulatory T cells (Tregs) within the mammal (e.g., within a targeted tissue within the mammal). For example, the methods and materials described herein can be used to increase the number of Tregs present within a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the number of Tregs present within a mammal does not decrease. In some cases, when treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein the treatment can be effective to reduce the number of activated T cells (e.g., CD4 ⁺ T cells and/or CD8 ⁺ T cells) within the mammal (e.g., within a targeted tissue within the mammal). For example, the methods and materials described herein can be used to reduce the number of activated T cells (e.g., CD4 ⁺ T cells and/or CD8 ⁺ T cells) present within a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the number of activated T cells (e.g., CD4 ⁺ T cells and/or CD8 ⁺ T cells) present within a mammal does not increase. In some cases, when treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein, the treatment can be effective to reduce the rate of T cell proliferation (e.g., activated T cell proliferation) within the mammal (e.g., within a targeted tissue within the mammal). For example, the methods and materials described herein can be used to reduce rate of T cell proliferation within a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the rate of T cell proliferation within a mammal does not increase. Any appropriate mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) can be treated as described herein. Examples of mammals that can be in need of immunosuppression and can be treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, mice, and rats. For example, one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be administered (e.g., by adoptive transfer) to a human having one or more autoimmune diseases to treat the human. Any appropriate one or more autoimmune diseases (e.g., GVHD) can be treated as described herein. Examples of autoimmune disease include, without limitation, GVHD, inflammatory bowel diseases (eg ulcerative colitis and Crohn’s disease) hepatitis bronchiolitis obliterans, pneumonitis, encephalitis, multiple sclerosis, rheumatoid arthritis, lupus, and psoriasis. In some cases, an autoimmune disease can be GVHD (e.g., acute GVHD or chronic GVHD). GVHD can be allogeneic GVHD (allo-GVHD) or autologous GVHD (auto-GVHD). GVHD can be any stage of GVHD. In some cases, GVHD can be associated with (e.g., following) a transplant. A transplant can be an allogeneic transplant or an autologous transplant. When treating a mammal having (or at risk of developing) GVHD, the mammal can have undergone any type of transplant (e.g., an allogeneic transplant such as bone marrow transplants, stem cell transplants, and organ transplants such as kidney transplants and liver transplants). In some cases, a mammal can be identified as having or at risk of developing one or more autoimmune diseases (e.g., GVHD). Any appropriate method can be used to identify a mammal as having or at risk of developing one or more autoimmune diseases (e.g., GVHD). In some cases, a mammal can be identified as having (or as being at risk of developing) GVHD. Any appropriate method for identifying a mammal as having (or as being at risk of developing) GVHD can be used. Once identified as having (or as being at risk of developing) GVHD, the mammal can be administered (e.g., by adoptive transfer) or instructed to self- administer one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) to treat the GVHD within the mammal. In some cases, one or more CAR-MSCs provided herein (e.g., one or more CAR- MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be administered (e.g., by adoptive transfer) to a mammal having or at risk of developing GVHD to reduce the severity of GVHD within the mammal. In some cases, reducing the severity of GVHD in a mammal can include reducing or eliminating one or more symptoms of GVHD (e.g., skin rashes, immune-mediated pneumonitis, intestinal inflammation, sloughing of the intestinal mucosal membrane, severe diarrhea, abdominal pain, nausea, vomiting, and/or elevated bilirubin levels). In some cases, reducing the severity of GVHD in a mammal can include reducing the stage of GVHD The stage of GVHD can be evaluated as described elsewhere (see, e.g., Jacobsohn et al., Orphanet. J. Rare Dis., 2:35 (2007)). Any appropriate method can be used to administer one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) to a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD). Examples of methods of administering MSCs provided herein to a mammal can include, without limitation, injection (e.g., intravenous, intraperitoneal, intramuscular, subcutaneous injection, or local injection into an area of inflammation). For example, a composition including one or more CAR-MSCs provided herein can be administered to a human by intravenous injection. In some cases, one or more CAR-MSCs provided herein (e.g., one or more CAR- MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be the sole active ingredient for treating a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD). For example, a composition including one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can include the one or more CAR-MSCs provided herein as the sole active agent to suppress an immune response within a mammal (e.g., a human) in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD). In some cases, one or more CAR-MSCs provided herein (e.g., one or more CAR- MSCs having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be administered in combination with one or more additional agents that can be used to treat a mammal (e.g., a human) in need of immunosuppression (eg a human having or at risk of developing one or more autoimmune diseases such as GVHD). In some cases, an agent that can be used to suppress an immune response can be an anti-inflammatory. In some cases, an agent that can be used to suppress an immune response can be an immunosuppressant. Examples of agents that can be used in combination with one or more CAR-MSCs provided herein include, without limitation, corticosteroids (e.g., prednisone and methylprednisolone), azathioprine, mercaptopurine, cyclosporine, infliximab, adalimumab, golimumab, and vedolizumab. In some cases, one or more CAR-MSCs provided herein can be administered at substantially the same time as one or more additional agents. For example, a composition including one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) also can include one or more additional agents that can be used to suppress an immune response within a mammal. In some cases, one or more CAR-MSCs provided herein can be administered first, and the one or more additional agents administered second, or vice versa. In some cases, one or more CAR-MSCs provided herein (e.g., one or more CAR- MSCs having an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides) can be used to treat a mammal (e.g., a human) having a disease or disorder that is not characterized by inflammation. For example, a CAR-MSC provided herein can be used to target a diseased tissue within a mammal (e.g., a human that is not in need of immunosuppression) to treat that diseased tissue. In some cases, a CAR-MSC provided herein can be used to target a degenerative tissue within a mammal (e.g., a human that is not in need of immunosuppression) to treat that tissue degeneration. For example, a CAR-MSC can express a CAR that can target a neural-specific antigen (e.g., AMPA) to target the MSC to neural tissues within a mammal (e.g., a mammal having a neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)) and includes a regenerative signaling domain (e.g., a BDNF signaling domain), and also can have (e.g., can be engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to treat the mammal In some cases a CAR MSC provided herein can be used to target a fibrotic tissue within a mammal (e.g., a human that is not in need of immunosuppression) to treat that fibrotic tissue. For example, a CAR-MSC can express a CAR that can target a cartilage-specific antigen (e.g., fibroblast activating protein (FAP) or signaling lymphocyte activation molecule-7 (SLAMF7, also referred to as CS-1)) to target the MSC to fibrotic tissues within a mammal (e.g., a mammal having one or more fibrotic diseases (e.g., cardiac fibrosis, hepatic fibrosis, pulmonary fibrosis, genital fibrosis, or skin fibrosis), and also can have (e.g., can be engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to treat the mammal. In some cases, a CAR-MSC provided herein can be used to target a cardiac tissue within a mammal (e.g., a human that is not in need of immunosuppression) to treat cardiac disease. For example, a CAR-MSC can express a CAR that can target a cardiac-specific antigen (e.g., HER2) to target the MSC to cardiac tissues within a mammal (e.g., a mammal having cardiac inflammation and/or cardiac degeneration) and includes a regenerative signaling domain (e.g., a VEGFR2 signaling domain), and also can have (e.g., can be engineered to have) an elevated level of one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides to treat the mammal. This document also provides kits containing one or more materials described herein. In some cases, a kit can include one or more CAR-MSCs provided herein (e.g., one or more CAR-MSCs having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides). For example, one or more CAR-MSCs provided herein can be combined with packaging material to form a kit. For example, one or more constructs (e.g., nucleic acid constructs) described herein (e.g., a construct encoding a CAR that can bind a tissue-specific antigen such as an epithelial-specific antigen and a construct encoding one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or one or more trafficking polypeptides) can be combined with packaging material to form a kit. The packaging material included in such a kit typically contains instructions or a label describing how the composition can be used for example in an adoptive transfer to treat a mammal in need of immunosuppression (e.g., a human having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein. In some cases, materials provided in kits described herein can be used for treating mammals (e.g., humans) having (or at risk of developing) GVHD as described herein. In some cases, the packaging material included in such a kit can contain instructions and/or a label describing how a composition described herein can be used. For example, a kit can contain instructions and/or a label describing how a composition described herein can be used to express one or more CARs and how to express one or more immunosuppressive polypeptides, one or more regenerative polypeptides, and/or one or more trafficking polypeptides in MSCs to engineer a CAR-MSC provided herein (e.g., a CAR-MSC having an elevated level one or more immunosuppressive polypeptides, an elevated level of one or more regenerative polypeptides, and/or an elevated level of one or more trafficking polypeptides). In some cases, the packaging material included in such a kit can contain instructions and/or a label describing how the CAR-MSCs provided herein can be used. For example, the packaging material included in such a kit can contain instructions and/or a label describing how the CAR-MSCs provided herein can be used in adoptive transfer to treat a mammal in need of immunosuppression (e.g., a having or at risk of developing one or more autoimmune diseases such as GVHD) as described herein. In some cases, a kit (e.g., a kit containing instructions and/or a label describing how the CAR-MSCs provided herein can be used in adoptive transfer) can include materials for use in an adoptive transfer procedure. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLES Example 1: Chimeric Antigen Receptor Engineering of Adipose Derived Mesenchymal Stromal Cells (CAR-MSCs) for Enhanced Immunosuppression Current MSC therapy can be ineffective due to suboptimal homing and immunosuppressive capacity following therapeutic administration. MSCs were lentivirally transduced to stably express CAR constructs and generate CAR-MSCs. This Example describes the design of CAR-MSCs expressing an Ecad-specific scFv to generate anti-Ecad CAR-MSC (EcCAR-MSC). The incorporation of a CD28 signaling domain in EcCAR-MSC resulted in improved T cell suppression in both tumor and GVHD models. Materials and Methods Cell lines, primary PBMC/T cells, and primary MSCs Primary human adipose derived (Ad)-MSCs were obtained and cultured with StemXVivo mesenchymal stromal cell expansion media (R&D Systems, Minneapolis, MN). Human epithelial breast cancer cell line, MCF7, was obtained from ATCC (CRL-3006, Manassas, VA, USA) and cultured in D10 (DMEM Gibco, Gaithersburg, MD, US) with 10% fetal bovine serum (FBS, Millipore Sigma, Ontario, Canada) and 1% Penicillin- Streptomycin-Glutamine (Gibco, Gaithersburg, MD, US). MCF7 was irradiated and confirmed for Ecad positivity by flow cytometry. Mantle cell lymphoma cell line JeKo-1 and acute lymphoblastic leukemia cell line Nalm6 were purchased from ATCC. JeKo-1 and Nalm6 cells were cultured in R10 (RPMI 1640, Gibco, Gaithersburg, MD, US) with 10% or 20% FBS (Millipore Sigma, Ontario, Canada), respectively, and 1% penicillin-streptomycin-glutamine (Gibco, Gaithersburg, MD, US). For in vivo experiment use, cell lines were transduced with luciferase-ZsGreen lentivirus (Addgene, Cambridge, MA, USA). Cell lines were cultured up to 10 passages, and fresh aliquots were thawed every 7–8 weeks. Cell lines were authenticated by the manufacturer and routinely checked for phenotype by flow cytometry. Cell lines were tested monthly for mycoplasma. Peripheral blood mononuclear cells (PBMC) were isolated from de-identified normal donor blood apheresis cones using SepMate tubes (STEMCELL Technologies, Vancouver, Canada). T cells were separated with negative selection magnetic beads using EasySepTM Human T Cell 80 Isolation Kit (STEMCELL Technologies). Primary T cells and PBMCs were cultured in T cell medium containing X-VIVO 15 (Lonza, Walkersville, MD, USA), 10% human serum albumin (Innovative Research, Novi, MI, USA), and 1% penicillin-streptomycin-glutamine (Gibco, Gaithersburg, MD, USA) before selection for in vitro coculture. Freshly isolated human PBMCs were injected via intravenous administration for in vivo experiments. CAR design and virus production MSCs were all transduced via lentiviral vector encoding specifically designed CAR construct under an EF1alpha promoter. Optimization of transduction was performed with a CART19 construct. The CAR19 used contained a CD19-directed scFv derived from clone FMC-63 fused to 41BB and CD3 ζ signaling domains (FMC63- 41BB-?). A VSV-g- pseudotyped 2nd generation lentivirus was generated by loading the lentivirus with the CAR19 transgene via lipofectamine transfection and transfecting into HEK-293T cells, followed by standard procedures for harvesting, concentration, and functional titration of lentivirus. CAR constructs were then designed to include a scFv against human/canine Ecad (Figure 6) with a CD28 intracellular signaling domain to induce MSC immunomodulatory activation (Figure 7). A CAR plasmid was generated, and sequence validated by Addgene (Watertown, MA, USA). Pre-seeded Ad-MSCs (concentration of 250,000 cells/well) were transduced in a 6-well plate with lentiviral particles at a multiplicity of infection (MOI) of 3 with various concentrations of protamine sulfate (25 µg/µL, 50 µg/µL, or 100 µg/µL) for optimization of CAR expression and MSC proliferation. T Cell suppression Assay The ability of CAR-MSCs to inhibit activated T cells was tested using a T cell suppression assay. Untransduced (UTD)-MSCs or EcCAR-MSCs (suppressors) were co- cultured with activated T cells (effectors) in the presence or absence of soluble Ecad (stimulator) to provide antigen-specific stimulation to the CAR-MSCs. T cells were isolated from PBMCs of normal donors using negative selection magnetic beads. Isolated T cells were non-specifically activated using CD3 stimulating beads at a 3:1 bead to T cell ratio in T cell medium containing X-VIVO 15 (Lonza, Walkersville, MD, USA), 10% human serum albumin (Innovative Research, Novi, MI, USA), and 1% penicillin-streptomycin-glutamine (Gibco, Gaithersburg, MD, USA). After 24 hours, stimulated T cells (effectors) were co- cultured with UTD-MSCs or EcCAR-MSCs (suppressors) alone or with soluble Ecad protein (stimulator) to activate EcCAR-MSCs specifically through the CAR in StemXVivo serum free mesenchymal stromal cell expansion media (R&D Systems, Minneapolis, MN, USA). Cells were co-cultured at 1:10 MSC to T cell ratios with 100,000 T cells per 96 well plate as indicated. Cells were then harvested and analyzed by flow cytometry after different co- culture timeline as indicated in individual experiments. Multichannel Flow Cytometry Staining for flow cytometry was performed. Briefly, MSCs were isolated and grown in culture, then transduced with CAR to create CAR-MSCs to be co-cultured with T cell / PBMC immune cells in 96 well plates for 24 hours and 6 well plates for longer term culture. Following desired co-culture durations, adherent MSC cells were detached with Accutase at 10 mL per 75 cm ² surface area and incubated for 10-15 minutes at 37°C. Following detachment, all well contents were spun, washed in flow buffer (PBS, 2% FBS v/v, and 1% sodium azide v/v), and stained with desired antibody mixes in the dark for 15 minutes. Following final wash steps, cells were analyzed for desired surface markers and positivity was determined through negative gating by Fluorescence Minus One (FMO) control wells. Absolute cell count numbers were obtained using volumetric measurement. Cells were gated on the following: SSC vs. FSC plots to for cell separation by size and complexity, FSC-H vs. FSC-A plots exclude doublets, SSC vs. V500 channel live/dead fixable aqua stain to exclude dead cells, followed by cell subset characterization based on predesigned antibody panels optimized and used to stain samples. Anti-human antibodies were purchased from Biolegend, eBioscience, or BD Biosciences (San Diego, CA, USA). Samples were prepared for flow cytometry as described elsewhere (see, e.g., Teshima et al., Biol Blood Marrow Transplant 22:11-16 (2016)). All antibodies used to stain samples are listed in Table 1. Flow cytometry was performed on three-laser CytoFLEX (Beckman Coulter, Chaska, MN, USA) where cells were gated by singlet discrimination, and live cells were determined by Live/Dead Aqua staining (L34966, Thermo Fisher Scientific, Waltham, MA, USA). All gating analyses were performed with FlowJo X10.0.7r2 software (Ashland, OR, USA) and Kaluza Analysis software (Indianapolis, Indiana, USA). Table 1. Antibodies. In Vivo Mouse Studies Female and male immunocompromised NOD-SCID-? ^-/- (NSG) mice were obtained from Jackson Laboratories at 6-8 weeks old. All cells were injected in 100 µL – 200 µLs of PBS via syringe through tail vein injection or intraperitoneal injection. Mice were imaged with a bioluminescent imager using an IVIS ^® Lumina S5 Imaging System (PerkinElmer, Hopkinton, MA, USA) to confirm engraftment of luciferase positive tumor model CD19 ⁺ Nalm6/JeKo1 cells in the cancer xenograft model or luciferase positive CAR-MSCs in the MSC persistence xenograft model. Imaging was performed 10?minutes after the intraperitoneal injection of 10?µL/g D-luciferin (15?mg/mL, Gold Biotechnology, St. Louis, MO, USA). In tumor mouse models, NSG mice were engrafted with the CD19 ⁺ luciferase ⁺ JeKo-1 or Nalm6 (1x10 ⁶ cells given i.v.). Engraftment was confirmed by bioluminescent imaging 1-2 weeks after injection. All mice then received irradiated Ecad ⁺ MCF-7 cells (5x10 ⁶ cells given i.p. to stimulate the EcCAR-MSCs) and CART19 cells (1x10 ⁶ cells given i.v. as a strategy to treat the CD19 ⁺ tumor). Mice were then randomized based on bioluminescent imaging as a measure of tumor burden to receive UTD-MSCs, EcCAR- MSCs, or no additional treatment (Figure 15). Serial bioluminescent imaging was subsequently performed to assess residual disease and determine antitumor activity of CART19 cells. In GVHD mouse models, GVHD was induced in NSG mice with allogeneic human PBMCs (20-30 x 10 ⁶ cells i.v.) and treated with either 1) UTD-MSCs or 2) CAR-MSCs (1 x 10 ⁶ cells i.p. on days 10 and 20) as well as 3) no MSC control mice (Figure 16). Body weight and clinical GVHD scoring (incorporating body weight, posture, diarrhea, activity, fur condition, and skin integrity) were monitored in all experiments for GVHD progression in each experimental group (n = 5). Mouse blood was collected by tail vein bleed (around 100 µL) with 70 µL of blood used for flow cytometry analysis. RBC lysis was applied using 1:10 BD FACS Lyse buffer (BD Biosciences, San Jose, CA, USA). Cells were then washed in flow buffer and incubated with their specific antibody mix at room temperature in the dark before flow analysis using CytoFLEX (Beckman Coulter, Chaska, MN, USA) was performed. The remainder of the blood was centrifuged at 13,000 rpm for 10 minutes to separate serum for cytokine analysis Canine Studies The Ecad-targeted CAR was based on a human/canine cross-reactive Ecad-directed scFv. This scFv was generated using phage display, and cross-reactivity with both dog and human Ecad was confirmed (Figure 7). EcCAR-MSCs were tested in healthy beagles. Subjects were injected i.p. with EcCAR-MSCs (1 x 10 ⁶ cells/kg). Subjects were followed daily, weights were monitored, and serial blood sampling was performed on colon biopsies on day 3 and examined by IHC for human CD105 ⁺ cells to assess MSC homing to canine Ecad ⁺ cells. RNA Isolation, Sequencing, and Analysis EcCAR-MSC or UTD-MSC cells were transduced accordingly in culture with or without recombinant human Ecad Fc chimera (BioLegend, San Diego, CA, USA) at 250 ng/mL as a form of CAR specific stimulation for 24 hours. Following in vitro culture, MSCs were detached for RNA isolation using a QIAGEN miRNeasy micro kit (Catalog no.217084, QIAGEN, Germantown, MD, USA). Bulk RNAseq was performed on MSCs from 3 different biological donor replicates in both UTD-MSC and EcCAR-MSC group to ensure rigor of results. Total RNA was prepped with a SMARTer stranded total RNA-seq kit v2, Pico input mammalian (Takara, Mountain View, CA, USA). Total RNA (three samples per lane) was sequenced on an Illumina HiSeq 4000 (Illumina, San Diego, CA, USA). Library preparation and sequencing were performed. Quality check was performed with FastQC v0.11.8 on sample generated FastQC files. Cutadapt v1.18 was used to trim and remove adapter sequences. Output files were confirmed for adaptor removal and quality using FastQC v0.11.8. Paired end reads from trimmed FastQ files were mapped to the latest human reference genome (GRCh38) downloaded from the NCBI databases. Genome index files were built and aligned with STAR v2.5.4b. Generic expression counts for each gene were generated with HTSeq (Python 3.6.5). Gene counts were normalized (geometric mean) and differential expression analysis was calculated with DESeq2 (R v3.6.1, R-project.org/) using adjusted p values <0.05 as statistical cut offs. Heatmaps were created using pheatmap (cran.r- project.org/web/packages/pheatmap/index.html) with PCAs generated with ggplot2 tools (cran.r-project.org/web/packages/ggplot2/index.html). Gene set enrichment analyses were performed using Enrichr. Protein-protein interaction networks were generated using QIAGEN Ingenuity Pathway Analysis. Cytokine Assays Cytokine assays were performed on mouse serum samples collected 15 days following MSC treatment or control treatment. Debris was removed from serum by centrifugation at 10,000 x g for 5 minutes. Serum was diluted 1:2 with serum matrix before plating and following the manufacturer’s protocol for Milliplex Human Cytokine/Chemokine MAGNETIC BEAD Premixed 38 Plex Kit (HCYTMAG-60K-PX38, Millipore Sigma, Ontario, Canada). Data were collected using a Luminex (Millipore Sigma, Ontario, Canada) and analyzed with Belysa Immunoassay Curve Fitting Software (Millipore Sigma, Ontario, Canada) and Microsoft Excel (Microsoft, Redmond, WA, USA). Significant findings were determined and reported with Prism Graph Pad (La Jolla, CA, USA). Statistical Analysis In vitro and in vivo experiments were performed using technical and biological replicates to allow for appropriate statistical analysis.2-way or 1-way ANOVA analyses were used to evaluate the differences between in vitro EcCAR-MSC and UTD-MSC surface marker expression by percent expression and T cell suppression capabilities by absolute T cell count evaluations. ANOVA analyses were also used to determine significant difference between in vivo EcCAR-MSC treated mice and UTD-MSC treated mice through IVIS imaging of luciferase positive tumors and luciferase positive MSCs, weight comparisons, blood composition by flow, and GVHD clinical score comparisons. Kaplan Meier survival analysis was used to determine significance of difference in survival outcomes in both tumor and GVHD Xenograft Models with Cox regression analyses used to adjust for confounders (e.g., sex). To make multiple comparisons between each individual group in each of the previously described analyses (above), Tukey’s multiple comparisons test was used as a supplement to ANOVA based analyses. For comparison between two groups, a two tailed unpaired Student’s t test was used in place of ANOVA. RNA-seq data was processed with DeSeq2 program where raw counts were normalized across the samples (geometric mean), and Benjamini-Hochberg procedure was used for multiple hypothesis correction. All relevant statistically significant comparisons were demarked with asterisks corresponding to levels of significance below p< 0.05 indicating a 95% confidence interval (where *p<0.05, **p<0.005, ***p<0.0005, and ****p<0.0001). End data points without asterisks represent not significant (ns) differences between groups. Relevant data depicts the mean of all data points with either standard deviation (s.d.) or standard error of the mean (SEM) used to determine error bars. Prism Graph Pad (La Jolla, CA, USA) and Microsoft Excel (Microsoft, Redmond, WA, USA) were used to analyze the experimental data. Results MSCs are successfully transduced to stably express CAR. Using polycation enhancer augmented lentiviral vectors, efficient transduction with stable expression of CAR into MSCs was established. Transduction using a CAR19 lentiviral vector was optimized as a proof of concept for CAR-MSC creation. The delivery of CAR- containing lentiviral particles was optimized for efficiency and cell survival with protamine sulfate enhancer. Using protamine sulfate enhancer and lentiviral MOI of 3, consistent CAR transduction efficiency of >70% was achieved (Figure 1A). Following transduction optimization using CAR19, alternative CAR designs were developed for CAR-MSC based autoimmune disease therapy. The primary CAR-MSC construct was directed to Ecad, a ligand expressed on inflamed intestinal epithelial cells involved in GVHD. As T cell migration is mediated by the interaction of CD103 (?E integrin) on the T cell surface with Ecad, which is universally expressed on all epithelial cells, it was determined whether redirecting MSCs to Ecad via CAR would protect host epithelial tissues by enhancing MSC specificity and activation at sites of inflammation in GVHD and other gut autoimmune diseases. Using phage display, several Ecad directed scFvs were generated and a human and canine cross reactive scFv was identified to enable testing in canine models (Figure 6). Using this clone, an Ecad-specific CAR construct was generated (Figure 7) and transduced into MSCs creating anti-Ecad CAR-MSCs (EcCAR-MSCs) with >90% transduction efficiency (Figure 1B). MSCs were derived from 5 different biological MSC donors (Table 2). Table 2. MSC donor profiles. MSC Donor Gender Age Race Sample o e e e e u osupp ess ve e ec s of CAR-MSCs could be enhanced through inclusion of specific intracellular signaling domains within the CAR, CD28 signaling was incorporated into the CAR-MSC construct design using a CD28 co-stimulated CAR backbone yielding a CAR targeting Ecad using a CD28ζ CAR backbone (EcCAR-MSCs) (Figure 7). It was also demonstrated that stable CAR expression in EcCAR-MSCs over multiple ex vivo passages (>3) was possible, and that >90% transduction efficiency was achieved across multiple MSC cell donors (Figures 1C-1D, see Table 3 for a description of GVHD clinical scoring system). To test the ability of EcCAR-MSCs to suppress activated T cells, T cell suppression assays were performed. UTD-MSCs or EcCAR-MSCs (suppressors) were co-cultured with activated T cells (effectors). EcCAR-MSCs induced superior suppression of T cells compared to UTD-MSCs in a dose-dependent manner (Figure 1E). The antigen- specific activation of EcCAR-MSCs was tested by measuring T cell suppression by EcCAR- MSCs in the presence or absence of Ecad protein to stimulate the anti-Ecad scFv on the CAR. To ensure reproducibility, both soluble Ecad and Ecad ⁺ MCF7 cell lines were used as a source of Ecad antigen. Both soluble and cell-based antigen-specific stimulation of EcCAR- MSCs resulted in enhanced suppression of T cells (Figures 1G-1G). Table 3. GVHD clinical scoring system. Grade Weight Loss Diarrhea Posture Activity Fur Texture Skin Integrity 0 < 10% No Normal Normal Normal Normal 1 10% - < 25% Yes Hunched Reduced Rufflings Flaked MSC engineering does not induce differentiation, and CAR-MSCs retain stemness. EcCAR-MSC stem phenotype and pathway enrichment was interrogated to identify unwanted differentiation induced by CAR-MSC engineering. Flow cytometry was used to study EcCAR-MSC stem phenotype (CD105 ⁺ , CD73 ⁺ , CD90 ⁺ , CD34-, CD14-, and CD45-), based on the minimum criteria for MSC stem maintenance set by the International Society of Cell Therapy (see, e.g., Dominici, et al., Cytotherapy 8, 315-317 (2006)). No significant differences between CAR-MSCs and UTD-MSCs were found (Figure 1H). Differential gene expression analysis by bulk RNA sequencing (RNAseq) comparing EcCAR-MSCs to UTD-MSCs was performed. Gene set enrichment analysis (GSEA) using CellMarker Augmented gene set revealed enrichment of adipose derived stem cell and unrestricted somatic stem cell subsets in EcCAR-MSCs (Figure 1I). Conversely, differentiated cell lineages such as smooth muscle, neural or vascular differentiation pathways were downregulated through GSEA (Figure 1J). These results indicate maintained stem phenotype following CAR-MSC engineering with limited differentiation induced by transduction or CAR expression. EcCAR-MSCs exhibit superior immunosuppression in tumor and GVHD models in vivo. To study the immunosuppressive functions of CAR-MSCs in vivo, multiple tumor and GVHD models were used to ensure reproducibility and rigor of results. For tumor xenograft models, CD19 ⁺ mantle cell lymphoma JeKo-1 and CD19 ⁺ acute lymphoblastic leukemia Nalm6 were used to test if CAR-MSCs suppressed the potent antitumor activity of CART19 cells (Figure 2A). Xenograft models were established through i.v. administration of either luciferase ⁺ JeKo-1 or luciferase ⁺ Nalm6 cells into immunocompromised NSG mice. Bioluminescent imaging was performed one week later to confirm engraftment, and mice were randomized to treatment with CART19 alone, CART19 in combination with UTD- MSCs or CART19 in combination with EcCAR MSCs Tumor burdens were assessed through biweekly bioluminescent imaging. Mice engrafted with Nalm6 and treated with CART19 plus EcCAR-MSCs displayed a high tumor burden (Figure 2B) and reduced overall survival compared to mice treated with CART19 plus UTD-MSCs or CART19 alone (Figure 2C). Similar results were demonstrated using Jeko-1 xenografts treated with CART19 plus EcCAR-MSCs or UTD-MSCs (Figures 8A-8B). Together, these data demonstrate superior effector T cell suppression by EcCAR-MSCs through increasing tumor burden and decreasing survival outcomes. A xenograft GVHD model was then generated through the i.v. administration of human PBMCs into NSG mice. In addition to PBMCs, mice were given PBS control, UTD- MSCs, or EcCAR-MSCs as GVHD treatment via intraperitoneal (i.p.) injection. Additional doses of MSCs or control treatment were administered i.p. every two weeks (Figure 2D). Mice were monitored for the development of clinical GVHD symptoms (e.g., diarrhea, motor function, posture, fur integrity, and skin integrity, body weight changes, and overall survival (see Table 3 for a description of GVHD clinical scoring system)). Peripheral blood was collected 14 days after the first dose of MSC treatment and analyzed for human T cell proliferation. EcCAR-MSC treatment led to prevention of weight loss (Figure 2E), amelioration of clinical GVHD (Figure 2F), suppression of T cell proliferation (Figure 2G), and improved overall survival (Figure 2H) compared to treatment with UTD-MSCs Together, these results indicate enhanced T cell suppression by EcCAR-MSCs, leading to the prevention of GVHD. EcCAR-MSCs display increases in critical transcription factors, suppressive cytokines, and inhibitory surface marker expression inducing an immunosuppressive milieu. To elucidate the mechanisms of enhanced EcCAR-MSC immunosuppression, CAR- MSCs were surveyed for unique transcriptional activation, cytokine secretion profiles, and surface markers characterizing their phenotype. To determine the impact of antigen specific CAR-MSC stimulation on the MSC transcriptome, RNAseq was performed on the following conditions: UTD-MSC (unstimulated), UTD-MSC (stimulated with soluble Ecad), EcCAR-MSC (unstimulated) and EcCAR-MSC (stimulated with soluble Ecad, to stimulate CAR-MSC through the CAR). To elucidate pathway activation intrinsic to EcCAR-MSC and stimulated EcCAR- MSC, comprehensive differential gene expression analysis was performed with the following comparisons: 1) EcCAR-MSC (unstimulated) vs. UTD-MSC (unstimulated) to account for intrinsic differences induced by EcCAR transduction and insertion, 2) EcCAR-MSC (stimulated with soluble Ecad) vs. EcCAR-MSC (unstimulated) to account for differences induced by antigen specific stimulation of EcCAR-MSC through the CAR’s scFv, 3) UTD- MSC (stimulated with soluble Ecad) vs. UTD-MSC (unstimulated) to serve as a control for potential Ecad-based stimulation in the absence of Ecad-specific CAR scFv. Unstimulated EcCAR-MSCs and UTD-MSCs (comparison 1) revealed distinct pathway activation with significant upregulation (at least 1.5-fold) of 355 genes in EcCAR-MSCs (Figure 3A and Figure 9). Differential gene expression analysis between Ecad-stimulated EcCAR-MSCs and unstimulated EcCAR-MSCs revealed more robust transcriptional activation with 1996 genes upregulated at least 1.5-fold (Figure 3A). This upregulation of nearly 6 times as many genes as comparison 1 highlights the functional capacity of CAR-based stimulation within the MSC (Figure 9). PCAs of expression profiles between Ecad-stimulated and unstimulated CAR- MSCs revealed clustering based on stimulation status (Figure 3B), while Ecad-stimulated and unstimulated UTD-MSCs (comparison 3) clustered solely by MSC biological donor (Figure 3C). GSEA of upregulated pathways characterized by CAR stimulation was more robustly linked to NFkB-mediated TNFα signaling pathways and IL-10 anti-inflammatory signaling pathways (Figure 3D). These pathways are related to canonical CD28 signaling through intracellular proteins binding to CD28 src-like domains, inducing nuclear activation of downstream functional cascades. Comparisons between unstimulated EcCAR-MSCs and UTD-MSCs were indicative of changes in signaling pathways inherent to the inclusion of CAR signaling domains and CAR transduction rather than stimulation of the CAR through its scFv. Transcriptomic analyses also demonstrated elevation of transcription factors NFkB1, JUN, RELB, and IRF1 in Ecad stimulated EcCAR-MSC (Figure 3E). To validate transcriptional findings, human cytokines were measured in the serum of UTD MSC and EcCAR MSC treated mice Analysis of serum cytokine composition 17 days following MSC administration supported RNAseq data with significant elevations of TNFα and IL-10 cytokines in EcCAR-MSC-treated mice compared to UTD-MSC-treated mice. Fibroblast Growth Factor 2 (FGF-2) was also elevated the serum of EcCAR-MSC- treated mice (Figure 4A and 10). To characterize MSC impact on human T cell subset composition in the mouse studies, peripheral blood was collected 14 and 31 days following UTD-MSC or EcCAR- MSC treatment in the GVHD xenograft model where weight loss was ameliorated following treatment with EcCAR-MSC (see Fig.2D). Analysis by flow cytometry revealed significant CD4 ⁺ and CD8 ⁺ human T cell suppression in the EcCAR-MSC treated group, correlating to sustained weight measurements (Figures 4B-4C). Analysis of CD4 ⁺ to CD8 ⁺ ratios revealed a propensity towards increased CD4 ⁺ T cell subsets and/or diminished CD8 ⁺ cytotoxic T cell subsets in EcCAR-MSC-treated mice as compared to UTD-MSC-treated mice (Figure 4D). Long-term analysis of blood on day 31 following MSC administration revealed a significant increase in percentage of Treg (human CD4 ⁺ , CD25 ⁺ , CD127-) cells in EcCAR-MSC-treated groups (Figure 4E). EcCAR-MSC surface marker expression was surveyed with CyTOF, which supported preservation of stem phenotype and revealed alterations in immunosuppressive surface markers and chemokines. Unlike UTD-MSCs, resting and Ecad-stimulated EcCAR-MSCs clustered into separate populations by surface marker-based t-distributed stochastic neighbor embedding statistical analysis indicating functional CAR antigen specific stimulation (Figures 4F-4G and 11). To test whether such distinct immunosuppressive surface marker profiles were maintained on EcCAR-MSCs following coculture with effector cells, additional surface marker characterization was performed on PBMC-cocultured MSCs through flow cytometry. EcCAR-MSCs and UTD-MSCs were stimulated with soluble Ecad and cocultured with PBMCs for 5 days before surface marker assessment. These results indicated distinct EcCAR-MSC surface marker upregulation of inhibitory receptors PD-1 and Galectin- 9(Gal-9) (Figure 4H). CXCR3 and CXCR4 homing chemokines were also elevated on stimulated EcCAR-MSCs (Figure 4I). This chemokine enhancement was supported by CXCR Chemokine Receptor Binding and Regulation of Leukocyte Chemotactic pathway enrichment in EcCAR MSC from RNAseq analysis (Figure 12) Collectively, these mechanistic assays indicated enhanced immunosuppressive functions intrinsic to EcCAR-MSC creation, but especially upon CAR stimulation. EcCAR-MSCs home to target sites and are safe in canine models. Canine models were used to ensure both homing capacity and safety of EcCAR-MSC administration using the canine cross-reactive EcCAR-MSCs (Figure 7). CAR-MSCs were designed with human and canine cross reactive anti-Ecad scFv to create EcCAR-MSC. EcCAR-MSCs were manufactured into human MSCs via lentiviral transduction and expanded in vitro until intraperitoneal injection into healthy canine subjects. EcCAR-MSC scFv-mediated homing to canine Ecad ⁺ cells was assessed through immunohistochemistry analysis. Subgroups were monitored for hematological and organ toxicity through blood assessment throughout the study. Healthy beagles were administered EcCAR-MSCs through i.p. injection. Colon biopsies were collected 3 and 28 days post-EcCAR-MSC administration evaluating canine Ecad ⁺ ligand and human CD105 ⁺ MSCs cells by immunohistochemistry (Figure 5A). Human CD105 ⁺ MSCs were present in colon tissues, overlapping with tissue regions of high canine Ecad expression, indicating target site homing (Figures 5B and 13). EcCAR-MSC toxicity was next assessed through serial measurements of complete blood counts, liver functions, kidney functions, and body weight. The administration of EcCAR- MSCs was not associated with weight loss, hematopoietic toxicity (Figure 5D), or organ toxicity (Figure 5E), indicating a strong safety profile. To study the expansion kinetics and persistence for further safety characterization of CAR-MSCs in vivo, luciferase ⁺ CAR-MSCs were generated to monitor expansion, persistence, and clearance of EcCAR-MSCs by serial bioluminescent imaging with and without antigen-specific stimulation through the co-administration of irradiated Ecad ⁺ MCF- 7 cells (Figure 14). Human PBMCs were administered to NSG mice, similar to the GVHD xenograft model. Mice were then treated with 1) luciferase ⁺ UTD-MSCs alone, 2) luciferase ⁺ UTD-MSCs plus irradiated Ecad ⁺ MCF-7 cells, 3) luciferase ⁺ EcCAR-MSCs alone, or 4) luciferase ⁺ EcCAR-MSCs plus the irradiated Ecad ⁺ MCF-7 cells (Figure 5G). Mice were then monitored with serial bioluminescent imaging every 2-3 days to detect MSC expansion and persistence. These studies revealed no difference between the clearance time (~25 days) of UTD-MSCs and EcCAR-MSCs, further supporting the safety profile of EcCAR-MSCs (Figure 5H-5I). Example 2: Exemplary Amino Acid Sequences Exemplary scFv sequences CDR sequences are indicated by bold and underlined font. Exemplary anti-Ecad scFv (also referred to as anti-hmcECAD.6) Heavy chain QVQLQESGPGLVKPSETLSLTCTVSGGSVSSYYWSWIRQPPGKGLEWIGHIYYSGNT NYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYFCARDRWNYYDSSPGYYYYY GMDVWGQGTTVTVSS (SEQ ID NO:1) Light chain LPVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSG VPDRFSGSKSGTSASLAISGLQSEDEADYYCASWDTSLRAWVFGGGTKLTVLG (SEQ ID NO:2) Exemplary anti-CD103 scFv Heavy chain QVQLQESGPGLVKPSETLSLTCTVSGGSVSSYYWSWIRQPPGKGLEWIGHIYYSGNT NYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYFCARDRWNYYDSSPGYYYYY GMDVWGQGTTVTVSS (SEQ ID NO:3) Light chain DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIFAASHLQS GVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQHNSSPFTFGPGTRVDIK (SEQ ID NO4) Exemplary anti-MOG scFv Heavy chain EVKLHESGAGLVKPGASVEISCKATGYTFSSFWIEWVKQRPGHGLEWIGEILPGRG RTNYNEKFKGKATFTAETSSNTAYMQLSSLTSEDSAVYYCATGNTMVNMPYWGQ GTTVTVSSGGGGSGGGGSGGGGS (SEQ ID NO:5) Light chain DIELTQSPSSLAVSAGEKVTMSCKSSQSLLNSGNQKNYLAWYQQKPGLPPKLLIYG ASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDHSYPLTFGAGTKLEIK (SEQ ID NO:6) Exemplary anti-AMPA scFv Heavy chain MKLPVLLVVLLLFTSPASSSEVQLQESGPSLVKPSQTLSLTCSVTGDSITSGFWNWLR KFPGNKLEYLGYINYSGSTYYNPSLKSRISFTRDTSKNQYYLHLNSVTAEDTATYYC ASWVLRDWGQGTTLTVSSARPTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVT LTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKK IEPRGPTIKPCPPCKCPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDV QISWFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEFKCKVNNKDL PAPIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNG KTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKS FSRTPGK (SEQ ID NO:7) Light chain MTSTLPFSPQVSTPRSKFATMEFQTQVLMSLLLCMSGAAADVVMTQTPLTLSVTIGQ PASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSKLDSGVPDRFTGSGSGT DFTLKISRVEAEDLGVYYCWQGTHFPQTFGGGTKLEIKRARADAAPTVSIFPPSSEQ LTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLT LTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC (SEQ ID NO:8) Exemplary anti-HER2 scFv EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTN GYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP (SEQ ID NO:27) Exemplary anti-FAP scFv Heavy chain QVQLQQSGAELARPGASVNLSCKASGYTFTNNGINWLKQRTGQGLEWIGEIYPRST NTLYNEKFKGKATLTADRSSNTAYMELRSLTSEDSAVYFCARTLTAPFAFWGQGT LVTVSA (SEQ ID NO:28) Light chain QIVLTQSPAIMSASPGEKVTMTCSASSGVNFMHWYQQKSGTSPKRWIFDTSKLASG VPARFSGSGSGTSYSLTISSMEAEDAATYYCQQWSFNPPTFGGGTKLEIKR (SEQ ID NO:29) Exemplary anti-CS1 scFv Heavy chain MGWSSIILFLVATATGVHSQVQLQQPGAELVRPGASVKLSCKASGYSFTTYWMNW VKQRPGQGLEWIGMIHPSDSETRLNQKFKDKATLTVDKSSSTA (SEQ ID NO:30) Light chain DIVMTQSQKSMSTSVGDRVSITCKASQDVITGVAWYQQKPGQSPKLLIYSASYRYT GVPDRFTGSGSGTDFTFTISNVQAEDLAVYYCQQHYSTPLTFGAGTKLELK (SEQ ID NO:31) Exemplary transmembrane domain sequences Exemplary CD28 transmembrane domain FWVLVVVGGVLACYSLLVTVAFIIFWV (SEQ ID NO:9) Exemplary CD8 transmembrane domain IYIWAPLAGTCGVLLLSLVITLYC (SEQ ID NO:32) Exemplary TLR3 transmembrane domain FFMINTSILLIFIFIVLLIHF (SEQ ID NO:72) Exemplary TLR4 transmembrane domain IGVSVLSVLVVSVVAVLVY (SEQ ID NO:73) Exemplary IFNGR1 transmembrane domain SLWIPVVAALLLFLVLSLVFI (SEQ ID NO:96) Exemplary IL10RA transmembrane domain VIIFFAFVLLLSGALAYCLAL (SEQ ID NO:97) Exemplary TLR9 transmembrane domain FALSLLAVALGLGVPMLHHLC (SEQ ID NO:98) Exemplary TNFR2 transmembrane domain FALPVGLIVGVTALGLLIIGVVNCVIMTQV (SEQ ID NO:99) Exemplary signaling domain sequences Exemplary 4-1BB signaling domain (SEQ ID NO:89) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL Exemplary TLR3 signaling domain EGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKED QSLKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAI EQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALG SKNSVH (SEQ ID NO:74) Exemplary TIR3 signaling domain WRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKEDQS LKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAIEQ NLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSK NSVHRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALH MQALPPR (SEQ ID NO:75) Exemplary TLR4 signaling domain KFYFHLMLLAGCIKYGRGE (SEQ ID NO:76) Exemplary TIR4 signaling domain NIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHK SRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRL LSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI (SEQ ID NO:77) Exemplary TLR4/TIR4 signaling domain KFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHY RDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFI V LQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGT VGTGCNWQEATSI (SEQ ID NO:100) Exemplary IFNGR1 signaling domain CFYIKKINPLKEKSIILPKSLISVVRSATLETKPESKYVSLITSYQPFSLEKEVVCEEPL S PATVPGMHTEDNPGKVEHTEELSSITEVVTTEENIPDVVPGSHLTPIERESSSPLSSNQ SEPGSIALNSYHSRNCSESDHSRNGFDTDSSCLESHSSLSDSEFPPNNKGEIKTEGQELI TVIKAPTSFGYDKPHVLVDLLVDDSGKESLIGYRPTEDSKEFS (SEQ ID NO:101) Exemplary IFN? signaling domain MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILK NWKEESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDD FEKLTNYSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRG (SEQ ID NO:78) Exemplary IL10RA signaling domain QLYVRRRKKLPSVLLFKKPSPFIFISQRPSPETQDTIHPLDEEAFLKVSPELKNLDLHGS TDSGFGSTKPSLQTEEPQFLLPDPHPQADRTLGNREPPVLGDSCSSGSSNSTDSGICLQ EPSLSPSTGPTWEQQVGSNSRGQDDSGIDLVQNSEGRAGDTQGGSALGHHSPPEPEV PGEEDPAAVAFQGYLRQTRCAEEKATKTGCLEEESPLTDGLGPKFGRCLVDEAGLH PPALAKGYLKQDPLEMTLASSGAPTGQWNQPTEEWSLLALSSCSDLGISDWSFAHD LAPLGCVAAPGGLLGSFNSDLVTLPLISSLQSSE (SEQ ID NO:102) Exemplary TLR9/TIR9 signaling domain GWDLWYCFHLCLAWLPWRGRQSGRDEDALPYDAFVVFDKTQSAVADWVYNELR GQLEECRGRWALRLCLEERDWLPGKTLFENLWASVYGSRKTLFVLAHTDRVSGLLR ASFLLAQQRLLEDRKDVVVLVILSPDGRRSRYVRLRQRLCRQSVLLWPHQPSGQRSF WAQLGMALTRDNHHFYNRNFCQGPTAE (SEQ ID NO:103) Exemplary TNFR2 signaling domain KKKPLCLQREAKVPHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTR NQPQAPGVEASGAGEARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQAS STMGDTDSSPSESPKDEQVPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKP S (SEQ ID NO:104) Exemplary CD28 signaling domain RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO:10) Exemplary CD3? signaling domain RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQ EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQAL PPR (SEQ ID NO:11) Exemplary BDNF signaling domain KLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIEN PQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAV KFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRN CLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVW SLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQRE PHMRKNIKGIHTLLQNLAKASPVYLDILG (SEQ ID NO:33) Exemplary VEGFR2 signaling domain LKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILI HIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFR QGKDYVGAIPVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEH LICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR KGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRR LKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELVEHLGN (SEQ ID NO:79) Exemplary hinge domain sequences Exemplary CD8 hinge domain TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO:34) Exemplary CD28 hinge domain LEPKSCDKTHTCPPCPDPK (SEQ ID NO:35) Exemplary leader sequences Exemplary leader polypeptide MALPVTALLLPLALLLHAARP (SEQ ID NO:36) Exemplary linker sequences Exemplary linker polypeptide EGKSSGSGSESKAS (SEQ ID NO:37) Exemplary polypeptide sequences Exemplary NFkB1 polypeptide MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFR FRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSL VGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGL LVHPDLAYLQAEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTG SFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIR FYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLET SEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGT GSTGPGYSFPHYGFPTYGGITFHPGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKN TVNLFGKVIETTEQDQEPSEATVGNGEVTLTYATGTKEESAGVQDNLFLEKAMQLA KRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHSQLVRDLLE VTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHL AAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMMSNSLPCLLLLVAAGAD VNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGST RLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMATSWQVFDIL NGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLGLGIL NNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQA HSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYG QEGPLEGKI (SEQ ID NO:12) Exemplary JUN polypeptide MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFR FRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSL VGKHCEDGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGL LVHPDLAYLQAEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTG SFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIR FYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLET SEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGT GSTGPGYSFPHYGFPTYGGITFHPGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKN TVNLFGKVIETTEQDQEPSEATVGNGEVTLTYATGTKEESAGVQDNLFLEKAMQLA KRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHSQLVRDLLE VTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRAGADLSLLDRLGNSVLHL AAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMMSNSLPCLLLLVAAGAD VNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGST RLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMATSWQVFDIL NGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLGLGIL NNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQA HSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYG QEGPLEGKI (SEQ ID NO:13) Exemplary RELB polypeptide MLRSGPASGPSVPTGRAMPSRRVARPPAAPELGALGSPDLSSLSLAVSRSTDELEIIDE YIKENGFGLDGGQPGPGEGLPRLVSRGAASLSTVTLGPVAPPATPPPWGCPLGRLVS PAPGPGPQPHLVITEQPKQRGMRFRYECEGRSAGSILGESSTEASKTLPAIELRDCGG LREVEVTACLVWKDWPHRVHPHSLVGKDCTDGICRVRLRPHVSPRHSFNNLGIQCV RKKEIEAAIERKIQLGIDPYNAGSLKNHQEVDMNVVRICFQASYRDQQGQMRRMDP VLSEPVYDKKSTNTSELRICRINKESGPCTGGEELYLLCDKVQKEDISVVFSRASWEG RADFSQADVHRQIAIVFKTPPYEDLEIVEPVTVNVFLQRLTDGVCSEPLPFTYLPRDH DSYGVDKKRKRGMPDVLGELNSSDPHGIESKRRKKKPAILDHFLPNHGSGPFLPPSA LLPDPDFFSGTVSLPGLEPPGGPDLLDDGFAYDPTAPTLFTMLDLLPPAPPHASAVVC SGGAGAVVGETPGPEPLTLDSYQAPGPGDGGTASLVGSNMFPNHYREAAFGGGLLS PGPEAT (SEQ ID NO:14) Exemplary IRF1 polypeptide YPYDVPDYAGTELGSTMASWSHPQFEKGGGSGGGSGGGSWSHPQFEKAADITSLYK KAGSTMPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKD ACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVR VYRMLPPLTKNQRKERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSY TVPGYMQDLEVEQALTPALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTS EATTDEDEEGKLPEDIMKLLEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEP EIDSPGGDIGLSLQRVFTDLKNMDATWLDSLLTPVRLPSIQAIPCAPLDPAFLYKVVT (SEQ ID NO:15) Exemplary TNF? polypeptide MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQ REEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANG VELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIK SPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRL (SEQ ID NO:16) Exemplary IL-10 polypeptide MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQ MKDQLDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSL GENLKTLRLRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIE AYMTMKIRN (SEQ ID NO:17) Exemplary FGF-2 polypeptide GGWLYHHSAGPAGRWRQRRVPAGPF*GSEAPVLQKRRLFPAHSPGWPCGRCA*EK RPAHQTATASGGTWCSEHQGCMR*PLSGDERRRPPAGEQMRHRRMFLLRTPGVQQ LQHVSLPQIHLLVRGSETHRPVQTGLQNRPWPESDPVPADVREIL (SEQ ID NO:18) Exemplary G-CSF polypeptide MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIP WAPLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFA TTIWQQMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLR HLAQP (SEQ ID NO:19) Exemplary GM-CSF polypeptide MWLQSLLLLGTVACSISAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETV EVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCA TQIITFESFKENLKDFLLVIPFDCWEPVQELPTFLYKVVGSTSGSGKPGSGEGSTKG (SEQ ID NO:20) Exemplary Eotaxin polypeptide MKVSAALLWLLLIAAAFSPQGLAGPASVPTTCCFNLANRKIPLQRLESYRRITSGKCP QKAVIFKTKLAKDICADPKKKWVQDSMKYLDQKSPTPKP (SEQ ID NO:21) Exemplary Gal-9 polypeptide AFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIA FHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMV NGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQPPGVWPANPAPITQTVIHTVQSAPG QMFSTPAIPPMMYPHPAYPMPFITTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIA FHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAV DGQHLFEYYHRLRNLPTINRLEVGGDIQLTHVQT Exemplary PD1 polypeptide MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSF SNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVR ARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV VGVVGGLLGSLVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSIVYASLD FQWREKTPEPPVPCVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCS WPLTRLQDIKLAVPRARDPPVAT (SEQ ID NO:23) Exemplary TIM-3 polypeptide MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKG ACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRI QIPGIMNDEKFNLKLVIKPAKVTPAPTLQRDFTAAFPRMLTTRGHGPAETQTLGSLPD INLTQISTLANELRDSRLANDLRDSGATIRIGIYIGAGICAGLALALIFGALIFKWYSHS KEKIQNLSLISLANLPPSGLANAVAEGIRSEENIYTIEENVYEVEEPNEYYCYVSSRQQ PSQPLGCRFAMP (SEQ ID NO:24) Exemplary CXCR3 polypeptide MVLEVSDHQVLNDAEVAALLENFSSSYDYGENESDSCCTSPPCPQDFSLNFDRAFLP ALYSLLFLLGLLGNGAVAAVLLSRRTALSSTDTFLLHLAVADTLLVLTLPLWAVDA AVQWVFGSGLCKVAGALFNINFYAGALLLACISFDRYLNIVHATQLYRRGPPARVTL TCLAVWGLCLLFALPDFIFLSAHHDERLNATHCQYNFPQVGRTALRVLQLVAGFLLP LLVMAYCYAHILAVLLVSRGQRRLRAMRLVVVVVVAFALCWTPYHLVVLVDILMD LGALARNCGRESRVDVAKSVTSGLGYMHCCLNPLLYAFVGVKFRERMWMLLLRL GCPNQRGLQRQPSSSRRDSSWSETSEASYSGL (SEQ ID NO:25) Exemplary CXCR4 polypeptide MEGISIYTSDNYTEEMGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVI LVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFGNFLCKAVHVI YTVNLYSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIF ANVSEADDRYICDRFYPNDLWVVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQ KRKALKTTVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWISITEALAFF H CCLNPILYAFLGAKFKTSAQHALTSVSRGSSLKILSKGKRGGHSSVSTESESSSFHSS (SEQ ID NO:26) Exemplary CTLA4 polypeptide MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFV CEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVN LTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVS SGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN (SEQ ID NO:91) Exemplary TLR3 polypeptide MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLN LTHNQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQL SDKTFAFCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHNGLSSTKLGTQVQLEN LQELLLSNNKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNV QLGPSLTEKLCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVV GNDSFAWLPQLEYFFLEYNNIQHLFSHSLHGLFNVRYLNLKRSFTKQSISLASLPKID DFSFQWLKCLEHLNMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLA HSPLHILNLTKNKISKIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLS YNKYLQLTRNSFALVPSLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANIN DDMLEGLEKLEILDLQHNNLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVE VFKDLFELKIIDLGLNNLNTLPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLT ELDMRFNPFDCTCESIAWFVNWINETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSC KDSAPFELFFMINTSILLIFIFIVLLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEY AAYIIHAYKDKDWVWEHFSSMEKEDQSLKFCLEERDFEAGVFELEAIVNSIKRSRKII FVITHHLLKDPLCKRFKVHHAVQQAIEQNLDSIILVFLEEIPDYKLNHALCLRRGMFK SHCILNWPVQKERIGAFRHKLQVALGSKNSVH Exemplary TLR4 polypeptide MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTK NLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSL ALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLT NLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTL RNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRL AYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTL KLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDL SFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFN GIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQ VLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQND FACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVS VLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELV KNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEI AQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRR LRKALLDGKSWNPEGTVGTGCNWQEATSI (SEQ ID NO:93) Exemplary TLR9 polypeptide MGFCRSALHPLSLLVQAIMLAMTLALGTLPAFLPCELQPHGLVNCNWLFLKSVPHFS MAAPRGNVTSLSLSSNRIHHLHDSDFAHLPSLRHLNLKWNCPPVGLSPMHFPCHMTI EPSTFLAVPTLEELNLSYNNIMTVPALPKSLISLSLSHTNILMLDSASLAGLHALRFLF MDGNCYYKNPCRQALEVAPGALLGLGNLTHLSLKYNNLTVVPRNLPSSLEYLLLSY NRIVKLAPEDLANLTALRVLDVGGNCRRCDHAPNPCMECPRHFPQLHPDTFSHLSRL EGLVLKDSSLSWLNASWFRGLGNLRVLDLSENFLYKCITKTKAFQGLTQLRKLNLSF NYQKRVSFAHLSLAPSFGSLVALKELDMHGIFFRSLDETTLRPLARLPMLQTLRLQM NFINQAQLGIFRAFPGLRYVDLSDNRISGASELTATMGEADGGEKVWLQPGDLAPAP VDTPSSEDFRPNCSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGS QFLPLTGLQVLDLSHNKLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVA HLRTLRHLSLAHNNIHSQVSQQLCSTSLRALDFSGNALGHMWAEGDLYLHFFQGLS GLIWLDLSQNRLHTLLPQTLRNLPKSLQVLRLRDNYLAFFKWWSLHFLPKLEVLDLA GNQLKALTNGSLPAGTRLRRLDVSCNSISFVAPGFFSKAKELRELNLSANALKTVDH SWFGPLASALQILDVSANPLHCACGAAFMDFLLEVQAAVPGLPSRVKCGSPGQLQG LSIFAQDLRLCLDEALSWDCFALSLLAVALGLGVPMLHHLCGWDLWYCFHLCLAW LPWRGRQSGRDEDALPYDAFVVFDKTQSAVADWVYNELRGQLEECRGRWALRLC LEERDWLPGKTLFENLWASVYGSRKTLFVLAHTDRVSGLLRASFLLAQQRLLEDRK DVVVLVILSPDGRRSRYVRLRQRLCRQSVLLWPHQPSGQRSFWAQLGMALTRDNH HFYNRNFCQGPTAE (SEQ ID NO:94) Exemplary TNFR2 polypeptide MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCC SKCSPGQHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQAC TREQNRICTCRPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAP GTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRS QHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVI MTQVKKKPLCLQREAKVPHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDR RAPTRNQPQAPGVEASGAGEARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQC SSQASSTMGDTDSSPSESPKDEQVPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDA GMKPS (SEQ ID NO:95) Example 3: Exemplary Nucleotide Sequences Nucleic acids encoding exemplary scFvs nucleic acid encoding an exemplary anti-Ecad scFv (also referred to as anti-hmcECAD.6) Heavy chain GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTG AGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATAGCATGAACTGGG TCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATTAGTAGTAGTA GTAGTACCATATACTACGTAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGA CAACGCCAAGAACTCACTGTATCTGCAAATGGACAGCCTGAGAGCCGAGGACAC GGCTGTGTATTACTGTGCGAGAGGAGGTCGGGTGTTAGTGGGAGCTCTATTTGAC TACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA (SEQ ID NO:38) Light chain CTGCCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTC ACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATTATGTCTACTGGT ACCAGCAACTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGGAATAATCAGC GGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTC CCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTGATTATTATTGTGCATCA TGGGATACCAGCCTGCGTGCCTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTC CTAGGT (SEQ ID NO:39) nucleic acid encoding an exemplary anti-CD103 scFv Heavy chain CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTG TCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGTAGTTACTATTGGAGCTGGA TCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGCCATATCTATTACAGTG GGAATACCAACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACA CGTCCAAGAATCAGTTCTCCCTGAAACTGAGCTCTGTGACCGCTGCGGACACGG CCGTGTATTTTTGTGCGAGAGATAGATGGAATTATTATGATAGTAGTCCCGGCTA TTATTATTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCAGC TCA (SEQ ID NO:40) Light chain GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAG TCACCATCACTTGCCGGGCGAGTCAGGGCATTAGAAATGATTTAGGCTGGTATCA GCAAAAACCAGGGAAAGCCCCTAAGCGCCTAATCTTTGCTGCATCCCATTTGCA AAGTGGAGTCCCTTCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCT CACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGCAT AATAGTTCCCCATTCACTTTCGGCCCTGGGACCAGAGTGGATATCAAA (SEQ ID NO:41) nucleic acid encoding an exemplary anti-MOG scFv Heavy chain GAGGTGAAGCTGCACGAGAGCGGCGCAGGTCTGGTGAAGCCCGGCGCCAGCGT GGAGATCAGCTGCAAGGCCACCGGCTACACCTTCAGCAGCTTCTGGATCGAGTG GGTGAAGCAGAGACCCGGCCACGGCCTGGAGTGGATCGGCGAGATCCTGCCCGG CAGAGGCAGAACCAACTACAACGAGAAGTTCAAGGGCAAGGCCACCTTCACCG CCGAGACCAGCAGCAACACCGCCTACATGCAGCTGAGCAGCCTGACCAGCGAGG ACAGCGCCGTGTACTACTGCGCCACCGGCAACACCATGGTGAACATGCCCTACT GGGGCCAGGGCACCACCGTGACCGTGAGCAGCGGTGGAGGTGGTTCGGGAGGT GGAGGTAGCGGAGGTGGTGGAAGC (SEQ ID NO:42) Light chain GATATTGAACTGACCCAGAGTCCCAGTAGCCTGGCCGTGAGTGCCGGCGAGAAA GTGACCATGAGCTGCAAAAGCAGCCAGAGCCTGCTGAACAGCGGCAACCAGAA AAACTACCTGGCCTGGTACCAGCAGAAACCCGGCCTGCCTCCTAAGCTGCTGAT CTACGGCGCCAGCACCAGAGAAAGCGGCGTGCCCGATAGATTCACCGGCTCTGG CTCTGGCACCGACTTCACCCTGACCATCAGCAGCGTGCAGGCCGAAGACCTGGC TGTCTACTACTGCCAGAACGACCACAGCTACCCCCTGACCTTCGGCGCCGGCACC AAGCTGGAGATCAAG (SEQ ID NO:43) nucleic acid encoding an exemplary anti-HER2 scFv GAAGTGCAGCTGGTGGAAAGCGGCGGCGGCCTGGTGCAGCCGGGCGGCAGCCT GCGCCTGAGCTGCGCGGCGAGCGGCTTTAACATTAAAGATACCTATATTCATTGG GTGCGCCAGGCGCCGGGCAAAGGCCTGGAATGGGTGGCGCGCATTTATCCGACC AACGGCTATACCCGCTATGCGGATAGCGTGAAAGGCCGCTTTACCATTAGCGCG GATACCAGCAAAAACACCGCGTATCTGCAGATGAACAGCCTGCGCGCGGAAGAT ACCGCGGTGTATTATTGCAGCCGCTGGGGCGGCGATGGCTTTTATGCGATGGATT ATTGGGGCCAGGGCACCCTGGTGACCGTGAGCAGCGCGAGCACCAAAGGCCCG AGCGTGTTTCCGCTGGCGCCGAGCAGCAAAAGCACCAGCGGCGGCACCGCGGCG CTGGGCTGCCTGGTGAAAGATTATTTTCCGGAACCGGTGACCGTGAGCTGGAAC AGCGGCGCGCTGACCAGCGGCGTGCATACCTTTCCGGCGGTGCTGCAGAGCAGC GGCCTGTATAGCCTGAGCAGCGTGGTGACCGTGCCGAGCAGCAGCCTGGGCACC CAGACCTATATTTGCAACGTGAACCATAAACCGAGCAACACCAAAGTGGATAAA AAAGTGGAACCG (SEQ ID NO:44) nucleic acid encoding an exemplary anti-FAP scFv Heavy chain CAGGTGCAGCTCCAGCAGAGTGGCGCAGAGCTCGCTCGCCCAGGCGCTTCTGTG AATCTGAGTTGTAAGGCCTCCGGATATACTTTTACGAACAACGGCATCAACTGGC TGAAGCAGCGGACCGGCCAGGGCCTGGAGTGGATCGGCGAAATATACCCCCGGT CCACAAACACTCTCTATAACGAGAAGTTTAAGGGCAAAGCAACTCTGACCGCGG ACAGGTCCTCTAACACAGCCTATATGGAGCTGAGAAGCTTGACGAGTGAGGACT CCGCTGTCTATTTTTGCGCCCGAACTCTGACCGCTCCTTTTGCTTTTTGGGGCCAG GGCACGCTCGTGACCGTAAGTGCG (SEQ ID NO:45) Light chain CAGATCGTCCTGACGCAGTCTCCAGCCATCATGAGCGCCTCACCCGGCGAAAAG GTGACCATGACCTGCTCAGCCTCTTCTGGTGTGAATTTCATGCACTGGTACCAGC AAAAAAGTGGGACCTCCCCTAAAAGGTGGATCTTCGATACCAGCAAACTGGCTT CTGGCGTTCCCGCAAGGTTTAGCGGCTCTGGTTCCGGCACATCATACAGCCTGAC GATCAGCAGCATGGAGGCAGAAGACGCAGCTACCTATTACTGCCAGCAATGGAG CTTTAACCCACCTACTTTCGGAGGAGGAACAAAGCTGGAAATAAAAAGA (SEQ ID NO:46) nucleic acid encoding an exemplary anti-CS1 scFv Heavy chain ATGGGATGGAGCTCTATCATCCTCTTCTTGGTAGCAACAGCTACAGGTGTCCACT CCCAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTGGTGAGGCCTGGAGCTTCAG TGAAGCTGTCCTGCAAGGCTTCGGGGTACTCCTTCACCACCTACTGGATGAACTG GGTGAAGCAGAGGCCTGGACAAGGCCTTGAGTGGATTGGCATGATTCATCCTTC CGATAGTGAAACTAGGTTAAATCAGAAGTTCAAGGACAAGGCCACATTGACTGT AGACAAATCCTCCAGCACAGCC (SEQ ID NO:47) Light chain GACATTGTGATGACCCAGTCTCAGAAATCCATGTCCACATCAGTAGGAGACAGG GTCAGCATCACCTGCAAGGCCAGTCAGGATGTTATTACTGGTGTAGCCTGGTATC AACAGAAACCAGGGCAATCTCCTAAATTACTGATTTACTCGGCATCCTACCGGTA CACTGGAGTCCCTGATCGCTTCACTGGCAGTGGATCTGGGACGGATTTCACTTTC ACCATCAGCAATGTGCAGGCTGAAGACCTGGCAGTTTATTACTGTCAGCAACATT ATAGTACTCCTCTCACTTTCGGTGCTGGGACCAAGCTGGAGCTGAAA (SEQ ID NO:48) nucleic acid encoding an exemplary anti-AMPA scFv Heavy chain ATGAAACTGCCGGTGCTGCTGGTGGTGCTGCTGCTGTTTACCAGCCCGGCGAGCA GCAGCGAAGTGCAGCTGCAGGAAAGCGGCCCGAGCCTGGTGAAACCGAGCCAG ACCCTGAGCCTGACCTGCAGCGTGACCGGCGATAGCATTACCAGCGGCTTTTGG AACTGGCTGCGCAAATTTCCGGGCAACAAACTGGAATATCTGGGCTATATTAACT ATAGCGGCAGCACCTATTATAACCCGAGCCTGAAAAGCCGCATTAGCTTTACCC GCGATACCAGCAAAAACCAGTATTATCTGCATCTGAACAGCGTGACCGCGGAAG ATACCGCGACCTATTATTGCGCGAGCTGGGTGCTGCGCGATTGGGGCCAGGGCA CCACCCTGACCGTGAGCAGCGCGCGCCCGACCGCGCCGAGCGTGTATCCGCTGG CGCCGGTGTGCGGCGATACCACCGGCAGCAGCGTGACCCTGGGCTGCCTGGTGA AAGGCTATTTTCCGGAACCGGTGACCCTGACCTGGAACAGCGGCAGCCTGAGCA GCGGCGTGCATACCTTTCCGGCGGTGCTGCAGAGCGATCTGTATACCCTGAGCA GCAGCGTGACCGTGACCAGCAGCACCTGGCCGAGCCAGAGCATTACCTGCAACG TGGCGCATCCGGCGAGCAGCACCAAAGTGGATAAAAAAATTGAACCGCGCGGC CCGACCATTAAACCGTGCCCGCCGTGCAAATGCCCGGCGCCGAACCTGCTGGGC GGCCCGAGCGTGTTTATTTTTCCGCCGAAAATTAAAGATGTGCTGATGATTAGCC TGAGCCCGATTGTGACCTGCGTGGTGGTGGATGTGAGCGAAGATGATCCGGATG TGCAGATTAGCTGGTTTGTGAACAACGTGGAAGTGCATACCGCGCAGACCCAGA CCCATCGCGAAGATTATAACAGCACCCTGCGCGTGGTGAGCGCGCTGCCGATTC AGCATCAGGATTGGATGAGCGGCAAAGAATTTAAATGCAAAGTGAACAACAAA GATCTGCCGGCGCCGATTGAACGCACCATTAGCAAACCGAAAGGCAGCGTGCGC GCGCCGCAGGTGTATGTGCTGCCGCCGCCGGAAGAAGAAATGACCAAAAAACA GGTGACCCTGACCTGCATGGTGACCGATTTTATGCCGGAAGATATTTATGTGGAA TGGACCAACAACGGCAAAACCGAACTGAACTATAAAAACACCGAACCGGTGCT GGATAGCGATGGCAGCTATTTTATGTATAGCAAACTGCGCGTGGAAAAAAAAAA CTGGGTGGAACGCAACAGCTATAGCTGCAGCGTGGTGCATGAAGGCCTGCATAA CCATCATACCACCAAAAGCTTTAGCCGCACCCCGGGCAAA (SEQ ID NO:49) Light chain ATGACCAGCACCCTGCCGTTTAGCCCGCAGGTGAGCACCCCGCGCAGCAAATTT GCGACCATGGAATTTCAGACCCAGGTGCTGATGAGCCTGCTGCTGTGCATGAGC GGCGCGGCGGCGGATGTGGTGATGACCCAGACCCCGCTGACCCTGAGCGTGACC ATTGGCCAGCCGGCGAGCATTAGCTGCAAAAGCAGCCAGAGCCTGCTGGATAGC GATGGCAAAACCTATCTGAACTGGCTGCTGCAGCGCCCGGGCCAGAGCCCGAAA CGCCTGATTTATCTGGTGAGCAAACTGGATAGCGGCGTGCCGGATCGCTTTACCG GCAGCGGCAGCGGCACCGATTTTACCCTGAAAATTAGCCGCGTGGAAGCGGAAG ATCTGGGCGTGTATTATTGCTGGCAGGGCACCCATTTTCCGCAGACCTTTGGCGG CGGCACCAAACTGGAAATTAAACGCGCGCGCGCGGATGCGGCGCCGACCGTGA GCATTTTTCCGCCGAGCAGCGAACAGCTGACCAGCGGCGGCGCGAGCGTGGTGT GCTTTCTGAACAACTTTTATCCGAAAGATATTAACGTGAAATGGAAAATTGATGG CAGCGAACGCCAGAACGGCGTGCTGAACAGCTGGACCGATCAGGATAGCAAAG ATAGCACCTATAGCATGAGCAGCACCCTGACCCTGACCAAAGATGAATATGAAC GCCATAACAGCTATACCTGCGAAGCGACCCATAAAACCAGCACCAGCCCGATTG TGAAAAGCTTTAACCGCAACGAATGC (SEQ ID NO:50) Nucleic acids encoding exemplary transmembrane domains nucleic acid encoding an exemplary CD28 transmembrane domain TTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAA CAGTGGCCTTTATTATTTTCTGGGTG (SEQ ID NO:51) nucleic acid encoding an exemplary CD8 transmembrane domain ATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGG TTATCACCCTTTACTGC (SEQ ID NO:52) nucleic acid encoding an exemplary TLR3 transmembrane domain TTTTTTATGATCAATACGTCTATTCTTCTCATATTTATTTTCATCGTTCTTCTGATT CACTTT (SEQ ID NO:80) nucleic acid encoding an exemplary TLR4 transmembrane domain ATTGGGGTGTCTGTCCTAAGCGTGCTGGTTGTTTCCGTGGTTGCCGTTCTGGTATA T (SEQ ID NO:81) nucleic acid encoding an exemplary IFNGR1 transmembrane domain TCTCTTTGGATTCCAGTTGTTGCTGCTTTACTACTCTTTCTAGTGCTTAGCCTGGT ATTCATC (SEQ ID NO:105) nucleic acid encoding an exemplary IL10RA transmembrane domain GTCATCATATTCTTTGCCTTTGTTTTGCTGCTCTCCGGAGCGCTGGCTTACTGCCT CGCGCTC (SEQ ID NO:106) nucleic acid encoding an exemplary TLR9 transmembrane domain TTTGCCCTCAGTCTTCTGGCTGTAGCTCTCGGGCTTGGCGTCCCTATGCTTCACCA CCTGTGT (SEQ ID NO:107) nucleic acid encoding an exemplary TNFR2 transmembrane domain TTCGCTCTTCCAGTTGGACTGATTGTGGGTGTGACAGCCTTGGGTCTACTAATAA TAGGAGTGGTGAACTGTGTCATCATGACCCAGGTG (SEQ ID NO:108) Nucleic acids encoding exemplary signaling domains nucleic acid encoding an exemplary CD28 signaling domain AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGC CGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTC GCAGCCTATCGCTCC (SEQ ID NO:53) nucleic acid encoding an exemplary CD3? signaling domain AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACAAGCAGGGCCAGAA CCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGA CAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACC CTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACA GTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTT TACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAG GCCCTGCCCCCTCGC (SEQ ID NO:54) nucleic acid encoding an exemplary 4-1BB signaling domain AAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCA GTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAA GAAGGAGGATGTGAACTG (SEQ ID NO:82) nucleic acid encoding an exemplary TLR3 signaling domain GAGGGGTGGAGGATTTCCTTTTACTGGAATGTGTCTGTGCATAGGGTTTTGGGTT TTAAGGAGATAGATCGCCAAACAGAGCAGTTCGAGTATGCAGCTTATATTATAC ACGCGTACAAAGATAAGGACTGGGTATGGGAGCATTTCAGTTCCATGGAAAAAG AAGACCAGTCCTTGAAGTTCTGCCTTGAAGAAAGGGACTTCGAGGCCGGGGTTT TTGAGCTGGAAGCGATCGTTAATAGTATTAAGCGGTCACGCAAGATCATCTTCGT AATAACACATCACCTCCTCAAGGATCCACTTTGCAAACGCTTCAAAGTTCACCAT GCGGTGCAGCAAGCGATCGAACAGAACCTTGACTCCATAATCCTTGTCTTTCTGG AAGAAATACCTGATTACAAGTTGAATCATGCTCTGTGTCTGCGGCGGGGAATGTT TAAGTCTCATTGTATCCTTAACTGGCCTGTGCAGAAAGAGCGCATTGGGGCGTTT AGGCATAAACTCCAGGTTGCGCTTGGAAGCAAAAATTCCGTTCAT (SEQ ID NO:83) nucleic acid encoding an exemplary TIR3 signaling domain TGGCGGATCTCTTTCTACTGGAACGTGTCAGTGCATAGAGTCCTCGGGTTCAAAG AGATTGACAGGCAGACGGAACAATTTGAGTATGCAGCGTACATTATCCATGCCT ACAAAGATAAAGACTGGGTTTGGGAACATTTCTCCTCCATGGAAAAGGAGGATC AGTCTTTGAAGTTTTGTCTGGAGGAGCGGGACTTTGAGGCGGGAGTGTTCGAGCT TGAGGCCATTGTAAACTCGATCAAGCGGTCCCGTAAAATCATCTTTGTGATAACA CACCACCTGTTGAAAGACCCGCTCTGCAAGCGCTTTAAGGTGCATCATGCTGTCC AGCAGGCCATCGAGCAGAATCTGGATTCAATTATTCTGGTGTTTTTAGAAGAGAT CCCAGACTATAAGCTGAATCACGCTCTATGTTTGCGTCGAGGCATGTTCAAATCT CATTGCATCTTGAATTGGCCGGTGCAAAAGGAAAGGATTGGTGCTTTTCGGCACA AATTGCAGGTCGCCCTGGGCTCCAAAAACAGTGTTCACAGAGTGAAGTTCAGCA GGAGCGCAGACGCCCCCGCGTACAAGCAGGGCCAGAACCAGCTCTATAACGAG CTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGG GACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTA CAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGA AAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGT ACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC TAAG (SEQ ID NO:84) nucleic acid encoding an exemplary TLR3/TIR3 signaling domain GAAGGATGGCGAATCTCTTTCTACTGGAACGTGTCTGTTCATAGAGTTTTGGGAT TCAAGGAAATAGATCGCCAAACCGAGCAATTCGAGTATGCCGCATATATCATAC ATGCATATAAGGACAAGGACTGGGTATGGGAACACTTCTCCTCTATGGAGAAAG AAGATCAGTCACTCAAATTCTGCTTGGAGGAACGAGATTTCGAAGCCGGTGTATT TGAGCTTGAAGCAATAGTAAACTCTATAAAAAGAAGTCGAAAAATTATTTTCGT CATCACACATCATCTGTTGAAGGACCCGCTTTGTAAGAGGTTTAAAGTGCATCAC GCTGTGCAGCAAGCCATTGAACAAAATCTGGATAGCATCATTCTCGTTTTTCTCG AAGAAATACCCGACTATAAGCTCAATCACGCTTTGTGCTTGCGACGGGGAATGTT CAAGTCCCACTGCATTCTTAACTGGCCAGTTCAAAAGGAACGAATCGGGGCCTT CAGACATAAATTGCAAGTTGCCCTGGGCTCAAAGAACTCAGTGCAC (SEQ ID NO:109) nucleic acid encoding an exemplary TLR4 signaling domain AAGTTCTATTTCCATCTGATGCTTCTCGCTGGCTGCATAAAGTACGGGAGGGGGG AG (SEQ ID NO:85) nucleic acid encoding an exemplary TIR4 signaling domain AATATATATGACGCTTTCGTGATCTACTCGAGCCAGGATGAGGACTGGGTTCGCA ACGAGCTAGTCAAGAATCTTGAAGAGGGCGTGCCTCCTTTCCAGCTCTGTCTGCA TTACCGCGATTTTATTCCTGGGGTGGCCATCGCGGCCAACATCATCCACGAGGGC TTCCATAAATCCAGAAAAGTGATTGTCGTTGTGAGCCAGCATTTCATCCAGTCCA GGTGGTGCATTTTCGAATATGAGATAGCCCAGACCTGGCAGTTTCTTAGCAGTCG GGCTGGGATTATTTTTATCGTGCTGCAGAAGGTTGAAAAGACCCTTTTGCGGCAA CAGGTGGAACTGTACCGATTATTATCCCGTAACACTTACTTGGAATGGGAAGACT CAGTTCTCGGACGCCACATTTTCTGGCGCCGGCTCAGGAAGGCCCTGCTGGATGG TAAATCCTGGAACCCCGAGGGGACAGTGGGGACCGGATGTAACTGGCAAGAGG CAACAAGTATA (SEQ ID NO:86) nucleic acid encoding an exemplary TLR4/TIR4 signaling domain AAGTTCTATTTCCATCTGATGCTTCTCGCTGGCTGCATAAAGTACGGGAGGGGGG AGAATATATATGACGCTTTCGTGATCTACTCGAGCCAGGATGAGGACTGGGTTCG CAACGAGCTAGTCAAGAATCTTGAAGAGGGCGTGCCTCCTTTCCAGCTCTGTCTG CATTACCGCGATTTTATTCCTGGGGTGGCCATCGCGGCCAACATCATCCACGAGG GCTTCCATAAATCCAGAAAAGTGATTGTCGTTGTGAGCCAGCATTTCATCCAGTC CAGGTGGTGCATTTTCGAATATGAGATAGCCCAGACCTGGCAGTTTCTTAGCAGT CGGGCTGGGATTATTTTTATCGTGCTGCAGAAGGTTGAAAAGACCCTTTTGCGGC AACAGGTGGAACTGTACCGATTATTATCCCGTAACACTTACTTGGAATGGGAAG ACTCAGTTCTCGGACGCCACATTTTCTGGCGCCGGCTCAGGAAGGCCCTGCTGGA TGGTAAATCCTGGAACCCCGAGGGGACAGTGGGGACCGGATGTAACTGGCAAGA GGCAACAAGTATA (SEQ ID NO:110) nucleic acid encoding an exemplary IFN? signaling domain ATGAAGTACACTTCTTACATACTCGCCTTCCAGCTTTGTATAGTGTTGGGCAGTCT GGGTTGCTATTGCCAAGATCCTTATGTGAAGGAAGCAGAAAATTTGAAGAAATA CTTTAACGCGGGTCATTCTGACGTTGCAGATAATGGAACCTTGTTTTTGGGAATA CTTAAAAATTGGAAGGAGGAAAGCGACCGCAAGATCATGCAGTCTCAAATCGTT TCCTTTTATTTTAAACTTTTCAAGAATTTTAAGGACGATCAGTCCATACAGAAAT CTGTAGAGACTATCAAAGAGGATATGAACGTAAAGTTTTTTAACAGCAACAAAA AGAAAAGAGATGACTTTGAGAAACTTACGAATTATAGTGTCACCGATCTGAACG TCCAACGCAAAGCAATCCACGAGTTGATTCAAGTTATGGCAGAGCTTTCCCCAG CGGCGAAAACTGGAAAGCGCAAACGATCTCAAATGCTCTTCCGGGGT (SEQ ID NO:87) nucleic acid encoding an exemplary IFNGR1 signaling domain TGTTTTTATATTAAGAAAATTAATCCATTGAAGGAAAAAAGCATAATATTACCCA AGTCCTTGATCTCTGTGGTAAGAAGTGCTACTTTAGAGACAAAACCTGAATCAAA ATATGTATCACTCATCACGTCATACCAGCCATTTTCCTTAGAAAAGGAGGTGGTC TGTGAAGAGCCGTTGTCTCCAGCAACAGTTCCAGGCATGCATACCGAAGACAAT CCAGGAAAAGTGGAACATACAGAAGAACTTTCTAGTATAACAGAAGTGGTGACT ACTGAAGAAAATATTCCTGACGTGGTCCCGGGCAGCCATCTGACTCCAATAGAG AGAGAGAGTTCTTCACCTTTAAGTAGTAACCAGTCTGAACCTGGCAGCATCGCTT TAAACTCGTATCACTCCAGAAATTGTTCTGAGAGTGATCACTCCAGAAATGGTTT TGATACTGATTCCAGCTGTCTGGAATCACATAGCTCCTTATCTGACTCAGAATTT CCCCCAAATAATAAAGGTGAAATAAAAACAGAAGGACAAGAGCTCATAACCGT AATAAAAGCCCCCACCTCCTTTGGTTATGATAAACCACATGTGCTAGTGGATCTA CTTGTGGATGATAGCGGTAAAGAGTCCTTGATTGGTTATAGACCAACAGAAGAT TCCAAAGAATTTTCATGAGATCAGCTAAGTTGCACCAACTTTGAAGTCTGATTTT CCTGGACAGTTTTCTGCTTTAATTTCATGAAAAGATTATGATCTCAGAAATTGTA TCTTAGTTGGTATCAACCAAATGGAGTGACTTAGTGTACATGAAAGCGTAAAGA GGATGTGTGGCATTTTCACTTTTGGCTTGTAAAGTACAGACTTTTTTTTTTTTTTA AACAAAAAAAGCATTGTAACTTATGAACCTTTACATCCAGATAGGTTACCAGTA ACGGAACAGTATCCAGTACTCCTGGTTCCTAGGTGAGCAGGTGATGCCCCAGGG ACCTTTGTAGCCACTTCACTTTTTTTCTTTTCTCTGCCTTGGTATAGCATATGTTTT TGTAAGTTTATGCATACAGTAATTTTAAGTAATTTCAGAAGAAATTCTGCAAGCT TTTCAAAATTGGACTTAAAATCTAATTCAAACTAATAGAATTAATGGAATATGTA AATAGAAACGTGTATATTTTTTATGAAACATTACAGTTAGAGATTTTTAAATAAA GAATTTTAAAACTCGAAAAAAAAAAAAAAAAAA (SEQ ID NO:111) nucleic acid encoding an exemplary IFN? signaling domain ATGAAGTACACTTCTTACATACTCGCCTTCCAGCTTTGTATAGTGTTGGGCAGTCT GGGTTGCTATTGCCAAGATCCTTATGTGAAGGAAGCAGAAAATTTGAAGAAATA CTTTAACGCGGGTCATTCTGACGTTGCAGATAATGGAACCTTGTTTTTGGGAATA CTTAAAAATTGGAAGGAGGAAAGCGACCGCAAGATCATGCAGTCTCAAATCGTT TCCTTTTATTTTAAACTTTTCAAGAATTTTAAGGACGATCAGTCCATACAGAAAT CTGTAGAGACTATCAAAGAGGATATGAACGTAAAGTTTTTTAACAGCAACAAAA AGAAAAGAGATGACTTTGAGAAACTTACGAATTATAGTGTCACCGATCTGAACG TCCAACGCAAAGCAATCCACGAGTTGATTCAAGTTATGGCAGAGCTTTCCCCAG CGGCGAAAACTGGAAAGCGCAAACGATCTCAAATGCTCTTCCGGGGT (SEQ ID NO:112) nucleic acid encoding an exemplary IL10RA signaling domain CAGCTCTATGTCAGAAGGAGAAAAAAGCTCCCGTCCGTGCTTCTTTTTAAGAAGC CTTCCCCGTTCATCTTCATTAGTCAGCGACCGAGCCCTGAGACCCAGGACACGAT CCATCCGCTTGATGAAGAGGCGTTTCTTAAGGTAAGCCCTGAACTGAAGAATCTC GATCTGCACGGCAGCACCGACAGTGGATTCGGGTCCACGAAACCCTCACTCCAG ACAGAAGAGCCTCAGTTTTTGTTGCCTGATCCTCACCCCCAGGCTGATAGAACGT TGGGTAATCGCGAGCCGCCGGTACTTGGAGACAGCTGCTCATCTGGGTCAAGCA ACTCAACGGATTCTGGGATATGTTTGCAGGAACCAAGCCTCTCACCTAGCACTGG GCCAACCTGGGAGCAGCAAGTGGGAAGCAATTCACGGGGGCAGGACGACTCTG GTATAGACCTGGTACAAAACTCTGAGGGACGGGCGGGAGATACTCAAGGTGGTA GCGCCCTGGGACACCACAGCCCACCGGAACCAGAGGTCCCGGGCGAGGAGGAC CCTGCAGCGGTGGCGTTTCAGGGATATTTGCGCCAAACCCGCTGTGCTGAGGAG AAGGCTACTAAAACGGGCTGCTTGGAAGAAGAATCTCCGCTCACAGACGGGCTC GGCCCGAAGTTCGGCCGATGTTTGGTGGACGAAGCGGGGCTTCATCCGCCGGCG CTTGCTAAAGGGTACCTGAAGCAAGACCCCTTGGAGATGACCCTGGCCTCCTCC GGGGCGCCTACTGGTCAGTGGAACCAGCCGACCGAGGAATGGTCTCTCCTCGCC CTTTCCAGTTGCTCCGACCTCGGTATATCAGACTGGAGTTTCGCACACGACCTTG CACCCCTCGGCTGTGTAGCCGCCCCAGGAGGCCTTCTTGGCTCATTTAACAGTGA CCTCGTTACGCTCCCCCTCATTTCATCTCTGCAATCCTCTGAA (SEQ ID NO:113) nucleic acid encoding an exemplary TLR9/TIR9 signaling domain GGCTGGGACCTCTGGTACTGCTTCCACCTGTGCCTGGCCTGGCTTCCCTGGCGGG GGCGGCAAAGTGGGCGAGATGAGGATGCCCTGCCCTACGATGCCTTCGTGGTCT TCGACAAAACGCAGAGCGCAGTGGCAGACTGGGTGTACAACGAGCTTCGGGGG CAGCTGGAGGAGTGCCGTGGGCGCTGGGCACTCCGCCTGTGCCTGGAGGAACGC GACTGGCTGCCTGGCAAAACCCTCTTTGAGAACCTGTGGGCCTCGGTCTATGGCA GCCGCAAGACGCTGTTTGTGCTGGCCCACACGGACCGGGTCAGTGGTCTCTTGCG CGCCAGCTTCCTGCTGGCCCAGCAGCGCCTGCTGGAGGACCGCAAGGACGTCGT GGTGCTGGTGATCCTGAGCCCTGACGGCCGCCGCTCCCGCTACGTGCGGCTGCGC CAGCGCCTCTGCCGCCAGAGTGTCCTCCTCTGGCCCCACCAGCCCAGTGGTCAGC GCAGCTTCTGGGCCCAGCTGGGCATGGCCCTGACCAGGGACAACCACCACTTCT ATAACCGGAACTTCTGCCAGGGACCCACGGCCGAATAG (SEQ ID NO:114) nucleic acid encoding an exemplary TNFR2 signaling domain AAAAAGAAGCCCTTGTGCCTGCAGAGAGAAGCCAAGGTGCCTCACTTGCCTGCC GATAAGGCCCGGGGTACACAGGGCCCCGAGCAGCAGCACCTGCTGATCACAGCG CCGAGCTCCAGCAGCAGCTCCCTGGAGAGCTCGGCCAGTGCGTTGGACAGAAGG GCGCCCACTCGGAACCAGCCACAGGCACCAGGCGTGGAGGCCAGTGGGGCCGG GGAGGCCCGGGCCAGCACCGGGAGCTCAGATTCTTCCCCTGGTGGCCATGGGAC CCAGGTCAATGTCACCTGCATCGTGAACGTCTGTAGCAGCTCTGACCACAGCTCA CAGTGCTCCTCCCAAGCCAGCTCCACAATGGGAGACACAGATTCCAGCCCCTCG GAGTCCCCGAAGGACGAGCAGGTCCCCTTCTCCAAGGAGGAATGTGCCTTTCGG TCACAGCTGGAGACGCCAGAGACCCTGCTGGGGAGCACCGAAGAGAAGCCCCT GCCCCTTGGAGTGCCTGATGCTGGGATGAAGCCCAGTTAACCAGGCCGGTGTGG GCTGTGTCGTAGCCAAGGTGGGCTGAGCCCTGGCAGGATGACCCTGCGAAG GGGCCCTGGTCCTTCCAGGCCCCCACCACTAGGACTCTGAGGCTCTTTCTGGGCC AAGTTCCTCTAGTGCCCTCCACAGCCGCAGCCTCCCTCTGACCTGCAGGCCAAGA GCAGAGGCAGCGAGTTGTGGAAAGCCTCTGCTGCCATGGCGTGTCCCTCTCGGA AGGCTGGCTGGGCATGGACGTTCGGGGCATGCTGGGGCAAGTCCCTGACTCTCT GTGACCTGCCCCGCCCAGCTGCACCTGCCAGCCTGGCTTCTGGAGCCCTTGGGTT TTTTGTTTGTTTGTTTGTTTGTTTGTTTGTTTCTCCCCCTGGGCTCTGCCCCAGCTC TGGCTTCCAGAAAACCCCAGCATCCTTTTCTGCAGAGGGGCTTTCTGGAGAGGAG GGATGCTGCCTGAGTCACCCATGAAGACAGGACAGTGCTTCAGCCTGAGGCTGA GACTGCGGGATGGTCCTGGGGCTCTGTGCAGGGAGGAGGTGGCAGCCCTGTAGG GAACGGGGTCCTTCAAGTTAGCTCAGGAGGCTTGGAAAGCATCACCTCAGGCCA GGTGCAGTGGCTCACGCCTATGATCCCAGCACTTTGGGAGGCTGAGGCGGGTGG ATCACCTGAGGTTAGGAGTTCGAGACCAGCCTGGCCAACATGGTAAAACCCCAT CTCTACTAAAAATACAGAAATTAGCCGGGCGTGGTGGCGGGCACCTATAGTCCC AGCTACTCAGAAGCCTGAGGCTGGGAAATCGTTTGAACCCGGGAAGCGGAGGTT GCAGGGAGCCGAGATCACGCCACTGCACTCCAGCCTGGGCGACAGAGCGAGAG TCTGTCTCAAAAGAAAAAAAAAAGCACCGCCTCCAAATGCCAACTTGTCCTTTTG TACCATGGTGTGAAAGTCAGATGCCCAGAGGGCCCAGGCAGGCCACCATATTCA GTGCTGTGGCCTGGGCAAGATAACGCACTTCTAACTAGAAATCTGCCAATTTTTT AAAAAAGTAAGTACCACTCAGGCCAACAAGCCAACGACAAAGCCAAACTCTGC CAGCCACATCCAACCCCCCACCTGCCATTTGCACCCTCCGCCTTCACTCCGGTGT GCCTGCAGCCCCGCGCCTCCTTCCTTGCTGTCCTAGGCCACACCATCTCCTTTCAG GGAATTTCAGGAACTAGAGATGACTGAGTCCTCGTAGCCATCTCTCTACTCCTAC CTCAGCCTAGACCCTCCTCCTCCCCCAGAGGGGTGGGTTCCTCTTCCCCACTCCC CACCTTCAATTCCTGGGCCCCAAACGGGCTGCCCTGCCACTTTGGTACATGGCCA GTGTGATCCCAAGTGCCAGTCTTGTGTCTGCGTCTGTGTTGCGTGTCGTGGGTGT GTGTAGCCAAGGTCGGTAAGTTGAATGGCCTGCCTTGAAGCCACTGAAGCTGGG ATTCCTCCCCATTAGAGTCAGCCTTCCCCCTCCCAGGGCCAGGGCCCTGCAGAGG GGAAACCAGTGTAGCCTTGCCCGGATTCTGGGAGGAAGCAGGTTGAGGGGCTCC TGGAAAGGCTCAGTCTCAGGAGCATGGGGATAAAGGAGAAGGCATGAAATTGTC TAGCAGAGCAGGGGCAGGGTGATAAATTGTTGATAAATTCCACTGGACTTGAGC TTGGCAGCTGAACTATTGGAGGGTGGGAGAGCCCAGCCATTACCATGGAGACAA GAAGGGTTTTCCACCCTGGAATCAAGATGTCAGACTGGCTGGCTGCAGTGACGT GCACCTGTACTCAGGAGGCTGAGGGGAGGATCACTGGAGCCCAGGAGTTTGAGG CTGCAGCGAGCTATGATCGCGCCACTACACTCCAGCCTGAGCAACAGAGTGAGA CCCTGTCTCTTAAAGAAAAAAAAAGTCAGACTGCTGGGACTGGCCAGGTTTCTG CCCACATTGGACCCACATGAGGACATGATGGAGCGCACCTGCCCCCTGGTGGAC AGTCCTGGGAGAACCTCAGGCTTCCTTGGCATCACAGGGCAGAGCCGGGAAGCG ATGAATTTGGAGACTCTGTGGGGCCTTGGTTCCCTTGTGTGTGTGTGTTGATCCC AAGACAATGAAAGTTTGCACTGTATGCTGGACGGCATTCCTGCTTATCAATAAAC CTGTTTGTTTTAA (SEQ ID NO:115) nucleic acid encoding an exemplary BDNF signaling domain AAACTGGCGCGCCATAGCAAATTTGGCATGAAAGGCCCGGCGAGCGTGATTAGC AACGATGATGATAGCGCGAGCCCGCTGCATCATATTAGCAACGGCAGCAACACC CCGAGCAGCAGCGAAGGCGGCCCGGATGCGGTGATTATTGGCATGACCAAAATT CCGGTGATTGAAAACCCGCAGTATTTTGGCATTACCAACAGCCAGCTGAAACCG GATACCTTTGTGCAGCATATTAAACGCCATAACATTGTGCTGAAACGCGAACTGG GCGAAGGCGCGTTTGGCAAAGTGTTTCTGGCGGAATGCTATAACCTGTGCCCGG AACAGGATAAAATTCTGGTGGCGGTGAAAACCCTGAAAGATGCGAGCGATAACG CGCGCAAAGATTTTCATCGCGAAGCGGAACTGCTGACCAACCTGCAGCATGAAC ATATTGTGAAATTTTATGGCGTGTGCGTGGAAGGCGATCCGCTGATTATGGTGTT TGAATATATGAAACATGGCGATCTGAACAAATTTCTGCGCGCGCATGGCCCGGA TGCGGTGCTGATGGCGGAAGGCAACCCGCCGACCGAACTGACCCAGAGCCAGAT GCTGCATATTGCGCAGCAGATTGCGGCGGGCATGGTGTATCTGGCGAGCCAGCA TTTTGTGCATCGCGATCTGGCGACCCGCAACTGCCTGGTGGGCGAAAACCTGCTG GTGAAAATTGGCGATTTTGGCATGAGCCGCGATGTGTATAGCACCGATTATTATC GCGTGGGCGGCCATACCATGCTGCCGATTCGCTGGATGCCGCCGGAAAGCATTA TGTATCGCAAATTTACCACCGAAAGCGATGTGTGGAGCCTGGGCGTGGTGCTGT GGGAAATTTTTACCTATGGCAAACAGCCGTGGTATCAGCTGAGCAACAACGAAG TGATTGAATGCATTACCCAGGGCCGCGTGCTGCAGCGCCCGCGCACCTGCCCGC AGGAAGTGTATGAACTGATGCTGGGCTGCTGGCAGCGCGAACCGCATATGCGCA AAAACATTAAAGGCATTCATACCCTGCTGCAGAACCTGGCGAAAGCGAGCCCGG TGTATCTGGATATTCTGGGC (SEQ ID NO:55) nucleic acid encoding an exemplary VEGFR2 signaling domain CTGAAGCTGGGCAAGCCCCTGGGCAGGGGCGCCTTCGGCCAGGTGATCGAGGCC GACGCCTTCGGCATCGACAAGACCGCCACCTGCAGGACCGTGGCCGTGAAGATG CTGAAGGAGGGCGCCACCCACAGCGAGCACAGGGCCCTGATGAGCGAGCTGAA GATCCTGATCCACATCGGCCACCACCTGAACGTGGTGAACCTGCTGGGCGCCTG CACCAAGCCCGGCGGCCCCCTGATGGTGATCGTGGAGTTCTGCAAGTTCGGCAA CCTGAGCACCTACCTGAGGAGCAAGAGGAACGAGTTCGTGCCCTACAAGACCAA GGGCGCCAGGTTCAGGCAGGGCAAGGACTACGTGGGCGCCATCCCCGTGGACCT GAAGAGGAGGCTGGACAGCATCACCAGCAGCCAGAGCAGCGCCAGCAGCGGCT TCGTGGAGGAGAAGAGCCTGAGCGACGTGGAGGAGGAGGAGGCCCCCGAGGAC CTGTACAAGGACTTCCTGACCCTGGAGCACCTGATCTGCTACAGCTTCCAGGTGG CCAAGGGCATGGAGTTCCTGGCCAGCAGGAAGTGCATCCACAGGGACCTGGCCG CCAGGAACATCCTGCTGAGCGAGAAGAACGTGGTGAAGATCTGCGACTTCGGCC TGGCCAGGGACATCTACAAGGACCCCGACTACGTGAGGAAGGGCGACGCCAGG CTGCCCCTGAAGTGGATGGCCCCCGAGACCATCTTCGACAGGGTGTACACCATC CAGAGCGACGTGTGGAGCTTCGGCGTGCTGCTGTGGGAGATCTTCAGCCTGGGC GCCAGCCCCTACCCCGGCGTGAAGATCGACGAGGAGTTCTGCAGGAGGCTGAAG GAGGGCACCAGGATGAGGGCCCCCGACTACACCACCCCCGAGATGTACCAGACC ATGCTGGACTGCTGGCACGGCGAGCCCAGCCAGAGGCCCACCTTCAGCGAGCTG GTGGAGCACCTGGGCAAC (SEQ ID NO:88) Nucleic acids encoding exemplary hinge domains nucleic acid encoding an exemplary CD28 hinge domain CTCGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCGGATCCC AAA (SEQ ID NO:56) nucleic acid encoding an exemplary CD8 hinge domain ACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAG CCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCAC ACGAGGGGGCTGGACTTCGCCTGTGAT (SEQ ID NO:57) Nucleic acids encoding exemplary polypeptides nucleic acid encoding an exemplary NFkB1 polypeptide ATGGCAGAAGATGATCCATATTTGGGAAGGCCTGAACAAATGTTTCATTTGGATC CTTCTTTGACTCATACAATATTTAATCCAGAAGTATTTCAACCACAGATGGCACT GCCAACAGCAGATGGCCCATACCTTCAAATATTAGAGCAACCTAAACAGAGAGG ATTTCGTTTCCGTTATGTATGTGAAGGCCCATCCCATGGTGGACTACCTGGTGCC TCTAGTGAAAAGAACAAGAAGTCTTACCCTCAGGTCAAAATCTGCAACTATGTG GGACCAGCAAAGGTTATTGTTCAGTTGGTCACAAATGGAAAAAATATCCACCTG CATGCCCACAGCCTGGTGGGAAAACACTGTGAGGATGGGATCTGCACTGTAACT GCTGGACCCAAGGACATGGTGGTCGGCTTCGCAAACCTGGGTATACTTCATGTG ACAAAGAAAAAAGTATTTGAAACACTGGAAGCACGAATGACAGAGGCGTGTAT AAGGGGCTATAATCCTGGACTCTTGGTGCACCCTGACCTTGCCTATTTGCAAGCA GAAGGTGGAGGGGACCGGCAGCTGGGAGATCGGGAAAAAGAGCTAATCCGCCA AGCAGCTCTGCAGCAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTCATGTT TACAGCTTTTCTTCCGGATAGCACTGGCAGCTTCACAAGGCGCCTGGAACCCGTG GTATCAGACGCCATCTATGACAGTAAAGCCCCCAATGCATCCAACTTGAAAATT GTAAGAATGGACAGGACAGCTGGATGTGTGACTGGAGGGGAGGAAATTTATCTT CTTTGTGACAAAGTTCAGAAAGATGACATCCAGATTCGATTTTATGAAGAGGAA GAAAATGGTGGAGTCTGGGAAGGATTTGGAGATTTTTCCCCCACAGATGTTCATA GACAATTTGCCATTGTCTTCAAAACTCCAAAGTATAAAGATATTAATATTACAAA ACCAGCCTCTGTGTTTGTCCAGCTTCGGAGGAAATCTGACTTGGAAACTAGTGAA CCAAAACCTTTCCTCTACTATCCTGAAATCAAAGATAAAGAAGAAGTGCAGAGG AAACGTCAGAAGCTCATGCCCAATTTTTCGGATAGTTTCGGCGGTGGTAGTGGTG CCGGAGCTGGAGGCGGAGGCATGTTTGGTAGTGGCGGTGGAGGAGGGGGCACT GGAAGTACAGGTCCAGGGTATAGCTTCCCACACTATGGATTTCCTACTTATGGTG GGATTACTTTCCATCCTGGAACTACTAAATCTAATGCTGGGATGAAGCATGGAAC CATGGACACTGAATCTAAAAAGGACCCTGAAGGTTGTGACAAAAGTGATGACAA AAACACTGTAAACCTCTTTGGGAAAGTTATTGAAACCACAGAGCAAGATCAGGA GCCCAGCGAGGCCACCGTTGGGAATGGTGAGGTCACTCTAACGTATGCAACAGG AACAAAAGAAGAGAGTGCTGGAGTTCAGGATAACCTCTTTCTAGAGAAGGCTAT GCAGCTTGCAAAGAGGCATGCCAATGCCCTTTTCGACTACGCGGTGACAGGAGA CGTGAAGATGCTGCTGGCCGTCCAGCGCCATCTCACTGCTGTGCAGGATGAGAA TGGGGACAGTGTCTTACACTTAGCAATCATCCACCTTCATTCTCAACTTGTGAGG GATCTACTAGAAGTCACATCTGGTTTGATTTCTGATGACATTATCAACATGAGAA ATGATCTGTACCAGACGCCCTTGCACTTGGCAGTGATCACTAAGCAGGAAGATG TGGTGGAGGATTTGCTGAGGGCTGGGGCCGACCTGAGCCTTCTGGACCGCTTGG GTAACTCTGTTTTGCACCTAGCTGCCAAAGAAGGACATGATAAAGTTCTCAGTAT CTTACTCAAGCACAAAAAGGCAGCACTACTTCTTGACCACCCCAACGGGGACGG TCTGAATGCCATTCATCTAGCCATGATGAGCAATAGCCTGCCATGTTTGCTGCTG CTGGTGGCCGCTGGGGCTGACGTCAATGCTCAGGAGCAGAAGTCCGGGCGCACA GCACTGCACCTGGCTGTGGAGCACGACAACATCTCATTGGCAGGCTGCCTGCTCC TGGAGGGTGATGCCCATGTGGACAGTACTACCTACGATGGAACCACACCCCTGC ATATAGCAGCTGGGAGAGGGTCCACCAGGCTGGCAGCTCTTCTCAAAGCAGCAG GAGCAGATCCCCTGGTGGAGAACTTTGAGCCTCTCTATGACCTGGATGACTCTTG GGAAAATGCAGGAGAGGATGAAGGAGTTGTGCCTGGAACCACGCCTCTAGATAT GGCCACCAGCTGGCAGGTATTTGACATATTAAATGGGAAACCATATGAGCCAGA GTTTACATCTGATGATTTACTAGCACAAGGAGACATGAAACAGCTGGCTGAAGA TGTGAAGCTGCAGCTGTATAAGTTACTAGAAATTCCTGATCCAGACAAAAACTG GGCTACTCTGGCGCAGAAATTAGGTCTGGGGATACTTAATAATGCCTTCCGGCTG AGTCCTGCTCCTTCCAAAACACTTATGGACAACTATGAGGTCTCTGGGGGTACAG TCAGAGAGCTGGTGGAGGCCCTGAGACAAATGGGCTACACCGAAGCAATTGAAG TGATCCAGGCAGCCTCCAGCCCAGTGAAGACCACCTCTCAGGCCCACTCGCTGC CTCTCTCGCCTGCCTCCACAAGGCAGCAAATAGACGAGCTCCGAGACAGTGACA GTGTCTGCGACAGCGGCGTGGAGACATCCTTCCGCAAACTCAGCTTTACCGAGTC TCTGACCAGTGGTGCCTCACTGCTAACTCTCAACAAAATGCCCCATGATTATGGG CAGGAAGGACCTCTAGAAGGCAAAATTTAG (SEQ ID NO:58) nucleic acid encoding an exemplary JUN polypeptide CGTGAAGTGACGGACTGTTCTATGACTGCAAAGATGGAAACGACCTTCTATGAC GATGCCCTCAACGCCTCGTTCCTCCCGTCCGAGAGCGGACCTTATGGCTACAGTA ACCCCAAGATCCTGAAACAGAGCATGACCCTGAACCTGGCCGACCCAGTGGGGA GCCTGAAGCCGCACCTCCGCGCCAAGAACTCGGACCTCCTCACCTCGCCCGACG TGGGGCTGCTCAAGCTGGCGTCGCCCGAGCTGGAGCGCCTGATAATCCAGTCCA GCAACGGGCACATCACCACCACGCCGACCCCCACCCAGTTCCTGTGCCCCAAGA ACGTGACAGATGAGCAGGAGGGCTTCGCCGAGGGCTTCGTGCGCGCCCTGGCCG AACTGCACAGCCAGAACACGCTGCCCAGCGTCACGTCGGCGGCGCAGCCGGTCA ACGGGGCAGGCATGGTGGCTCCCGCGGTAGCCTCGGTGGCAGGGGGCAGCGGC AGCGGCGGCTTCAGCGCCAGCCTGCACAGCGAGCCGCCGGTCTACGCAAACCTC AGCAACTTCAACCCAGGCGCGCTGAGCAGCGGCGGCGGGGCGCCCTCCTACGGC GCGGCCGGCCTGGCCTTTCCCGCGCAACCCCAGCAGCAGCAGCAGCCGCCGCAC CACCTGCCCCAGCAGATGCCCGTGCAGCACCCGCGGCTGCAGGCCCTGAAGGAG GAGCCTCAGACAGTGCCCGAGATGCCCGGCGAGACACCGCCCCTGTCCCCCATC GACATGGAGTCCCAGGAGCGGATCAAGGCGGAGAGGAAGCGCATGAGGAACCG CATCGCTGCCTCCAAGTGCCGAAAAAGGAAGCTGGAGAGAATCGCCCGGCTGGA GGAAAAAGTGAAAACCTTGAAAGCTCAGAACTCGGAGCTGGCGTCCACGGCCA ACATGCTCAGGGAACAGGTGGCACAGCTTAAACAGAAAGTCATGAACCACGTTA ACAGTGGGTGCCAACTCATGCTAACGCAGCAGTTGCAAACATTTTGA (SEQ ID NO:59) nucleic acid encoding an exemplary RELB polypeptide ATGCTTCGGTCTGGGCCAGCCTCTGGGCCGTCCGTCCCCACTGGCCGGGCCATGC CGAGTCGCCGCGTCGCCAGACCGCCGGCTGCGCCGGAGCTGGGGGCCTTAGGGT CCCCCGACCTCTCCTCACTCTCGCTCGCCGTTTCCAGGAGCACAGATGAATTGGA GATCATCGACGAGTACATCAAGGAGAACGGCTTCGGCCTGGACGGGGGACAGCC GGGCCCGGGCGAGGGGCTGCCACGCCTGGTGTCTCGCGGGGCTGCGTCCCTGAG CACGGTCACCCTGGGCCCTGTGGCGCCCCCAGCCACGCCGCCGCCTTGGGGCTG CCCCCTGGGCCGACTAGTGTCCCCAGCGCCGGGCCCGGGCCCGCAGCCGCACCT GGTCATCACGGAGCAGCCCAAGCAGCGCGGCATGCGCTTCCGCTACGAGTGCGA GGGCCGCTCGGCCGGCAGCATCCTTGGGGAGAGCAGCACCGAGGCCAGCAAGA CGCTGCCCGCCATCGAGCTCCGGGATTGTGGAGGGCTGCGGGAGGTGGAGGTGA CTGCCTGCCTGGTGTGGAAGGACTGGCCTCACCGAGTCCACCCCCACAGCCTCGT GGGGAAAGACTGCACCGACGGCATCTGCAGGGTGCGGCTCCGGCCTCACGTCAG CCCCCGGCACAGTTTTAACAACCTGGGCATCCAGTGTGTGAGGAAGAAGGAGAT TGAGGCTGCCATTGAGCGGAAGATTCAACTGGGCATTGACCCCTACAACGCTGG GTCCCTGAAGAACCATCAGGAAGTAGACATGAATGTGGTGAGGATCTGCTTCCA GGCCTCATATCGGGACCAGCAGGGACAGATGCGCCGGATGGATCCTGTGCTTTC CGAGCCCGTCTATGACAAGAAATCCACAAACACATCAGAGCTGCGGATTTGCCG AATTAACAAGGAAAGCGGGCCGTGCACCGGTGGCGAGGAGCTCTACTTGCTCTG CGACAAGGTGCAGAAAGAGGACATATCAGTGGTGTTCAGCAGGGCCTCCTGGGA AGGTCGGGCTGACTTCTCCCAGGCCGACGTGCACCGCCAGATTGCCATTGTGTTC AAGACGCCGCCCTACGAGGACCTGGAGATTGTCGAGCCCGTGACAGTCAACGTC TTCCTGCAGCGGCTCACCGATGGGGTCTGCAGCGAGCCATTGCCTTTCACGTACC TGCCTCGCGACCATGACAGCTACGGCGTGGACAAGAAGCGGAAACGGGGGATG CCCGACGTCCTTGGGGAGCTGAACAGCTCTGACCCCCATGGCATCGAGAGCAAA CGGCGGAAGAAAAAGCCGGCCATCCTGGACCACTTCCTGCCCAACCACGGCTCA GGCCCGTTCCTCCCGCCGTCAGCCCTGCTGCCAGACCCTGACTTCTTCTCTGGCA CCGTGTCCCTGCCCGGCCTGGAGCCCCCTGGCGGGCCTGACCTCCTGGACGATGG CTTTGCCTACGACCCTACGGCCCCCACACTCTTCACCATGCTGGACCTGCTGCCC CCGGCACCGCCACACGCTAGCGCTGTTGTGTGCAGCGGAGGTGCCGGGGCCGTG GTTGGGGAGACCCCCGGCCCTGAACCACTGACACTGGACTCGTACCAGGCCCCG GGCCCCGGGGATGGAGGCACCGCCAGCCTTGTGGGCAGCAACATGTTCCCCAAT CATTACCGCGAGGCGGCCTTTGGGGGCGGCCTCCTATCCCCGGGGCCTGAAGCC ACG (SEQ ID NO:60) nucleic acid encoding an exemplary IRF1 polypeptide TACCCATACGATGTTCCTGACTATGCCGGTACCGAGCTCGGATCCACCATGGCTA GCTGGAGCCACCCGCAGTTCGAGAAAGGTGGAGGTTCCGGAGGTGGATCGGGAG GTGGATCGTGGAGCCACCCGCAGTTCGAAAAAGCGGCCGATATCACAAGTTTGT ACAAAAAAGCAGGCTCCACCATGCCCATCACTCGGATGCGCATGAGACCCTGGC TAGAGATGCAGATTAATTCCAACCAAATCCCGGGGCTCATCTGGATTAATAAAG AGGAGATGATCTTCCAGATCCCATGGAAGCATGCTGCCAAGCATGGCTGGGACA TCAACAAGGATGCCTGTTTGTTCCGGAGCTGGGCCATTCACACAGGCCGATACA AAGCAGGGGAAAAGGAGCCAGATCCCAAGACGTGGAAGGCCAACTTTCGCTGT GCCATGAACTCCCTGCCAGATATCGAGGAGGTGAAAGACCAGAGCAGGAACAA GGGCAGCTCAGCTGTGCGAGTGTACCGGATGCTTCCACCTCTCACCAAGAACCA GAGAAAAGAAAGAAAGTCGAAGTCCAGCCGAGATGCTAAGAGCAAGGCCAAGA GGAAGTCATGTGGGGATTCCAGCCCTGATACCTTCTCTGATGGACTCAGCAGCTC CACTCTGCCTGATGACCACAGCAGCTACACAGTTCCAGGCTACATGCAGGACTT GGAGGTGGAGCAGGCCCTGACTCCAGCACTGTCGCCATGTGCTGTCAGCAGCAC TCTCCCCGACTGGCACATCCCAGTGGAAGTTGTGCCGGACAGCACCAGTGATCT GTACAACTTCCAGGTGTCACCCATGCCCTCCACCTCTGAAGCTACAACAGATGAG GATGAGGAAGGGAAATTACCTGAGGACATCATGAAGCTCTTGGAGCAGTCGGAG TGGCAGCCAACAAACGTGGATGGGAAGGGGTACCTACTCAATGAACCTGGAGTC CAGCCCACCTCTGTCTATGGAGACTTTAGCTGTAAGGAGGAGCCAGAAATTGAC AGCCCAGGGGGGGATATTGGGCTGAGTCTACAGCGTGTCTTCACAGATCTGAAG AACATGGATGCCACCTGGCTGGACAGCCTGCTGACCCCAGTCCGGTTGCCCTCCA TCCAGGCCATTCCCTGTGCACCGTTGGACCCAGCTTTCTTGTACAAAGTGGTGAC GTAA (SEQ ID NO:61) nucleic acid encoding an exemplary TNF? polypeptide ATGTCTACCGAGTCTATGATTAGGGACGTGGAACTGGCTGAGGAGGCACTGCCC AAAAAAACCGGCGGACCACAGGGCTCTAGGAGATGTCTGTTTCTGTCTCTGTTCT CTTTTCTCATCGTGGCTGGCGCTACAACACTCTTCTGTCTGCTCCATTTCGGCGTG ATTGGACCACAGCGAGAGGAATTTCCCCGGGATCTGTCACTCATTTCACCACTGG CACAGGCTGTCCGATCTTCATCTCGGACTCCATCCGACAAACCTGTCGCCCATGT CGTCGCCAACCCACAGGCCGAGGGCCAGCTCCAGTGGCTCAATAGGAGGGCAAA CGCTCTGCTCGCCAATGGCGTGGAACTCCGGGATAACCAGCTCGTCGTGCCTAGT GAGGGACTGTACCTCATCTACTCCCAGGTGCTGTTTAAGGGCCAGGGATGTCCTT CTACACATGTGCTGCTCACACACACAATTTCACGGATCGCCGTGTCTTACCAGAC TAAAGTCAATCTGCTCTCTGCCATCAAATCCCCATGTCAGCGGGAAACACCTGAG GGCGCTGAGGCTAAACCTTGGTACGAACCCATCTACCTCGGAGGCGTGTTCCAG CTGGAGAAGGGCGATAGACTGA (SEQ ID NO:62) nucleic acid encoding an exemplary IL-10 polypeptide ATGCACAGCTCAGCACTGCTCTGTTGCCTGGTCCTTCTGACAGGCGTAAGGGCGT CACCTGGCCAAGGAACACAGTCAGAGAACAGCTGTACACATTTCCCCGGCAACT TGCCCAATATGCTTAGGGATCTTCGCGATGCCTTCTCACGAGTGAAGACATTTTT CTTCAAGGGATACCTCGGATGCCAGGCACTGAGCGAAATGATACAGTTCTACCT GGAAGAGGTAATGCCTCAGGCAGAAAATCAGGACCCCGATATTAAAGCTCATGT GAACTCTCTGGGTGAGAACCTGAAAACTCTGAGGCTGAGGCTGCGGAGGTGTCA CAGATTCCTGCCATGCGAGAACAAATCAAAAGCCGTCGAACAGGTGAAGAACGC CTTTAACAAACTGCAGGAGAAAGGCATCTATAAAGCGATGAGCGAGTTCGATAT TTTCATCAACTACATTGAGGCATACATGACGATGAAAATCCGAAATTAG (SEQ ID NO:63) nucleic acid encoding an exemplary FGF-2 polypeptide GGCGGCTGGCTCTATCACCACTCTGCCGGCCCTGCCGGAAGATGGCGGCAGCGG CGCGTTCCCGCCGGGCCATTTTAAGGATCCGAAGCGCCTGTACTGCAAAAACGG CGGCTTTTTCCTGCGCATTCACCCGGATGGCCGTGTGGACGGTGTGCGTGAGAAA AGCGACCCGCACATCAAACTGCAACTGCAAGCGGAGGAACGTGGTGTAGTGAGC ATCAAGGGTGTATGCGCTAACCGTTATCTGGCGATGAAAGAAGACGGCCGCCTG CTGGCGAGCAAATGCGTCACCGACGAATGTTTCTTCTTCGAACGCCTGGAGTCCA ACAACTACAACACGTATCGCTCCCGCAAATACACCTCTTGGTACGTGGCTCTGAA ACGCACCGGCCAGTACAAACTGGGCTCCAAAACCGGCCCTGGCCAGAAAGCGAT CCTGTTCCTGCCGATGTCCGCGAAATCCTAA (SEQ ID NO:64) nucleic acid encoding an exemplary G-CSF polypeptide ATGACTCCTTTGGGTCCAGCTTCTTCCTTGCCTCAATCCTTCTTGTTGAAGTGTTT GGAGCAGGTTAGAAAGATCCAGGGTGATGGTGCTGCTTTGCAAGAGAAGTTGTG TGCTACTTACAAGTTGTGTCACCCAGAAGAGTTGGTTTTGTTGGGTCACTCCTTG GGTATTCCTTGGGCTCCATTGTCCTCTTGTCCATCCCAAGCTTTGCAATTGGCTGG TTGTTTGTCCCAATTGCACTCCGGTTTGTTCTTGTACCAGGGTTTGTTGCAAGCTT TGGAGGGTATTTCTCCAGAGTTGGGTCCAACTTTGGACACATTGCAGTTGGACGT TGCTGACTTCGCTACTACTATCTGGCAACAGATGGAAGAATTGGGTATGGCTCCA GCTTTGCAGCCAACTCAAGGTGCTATGCCAGCTTTTGCTTCTGCTTTCCAGAGAA GAGCTGGTGGTGTTTTGGTTGCTTCTCACTTGCAGTCTTTCTTGGAGGTTTCCTAC AGAGTTTTGAGACACTTGGCTCAACCATAA (SEQ ID NO:65) nucleic acid encoding an exemplary GM-CSF polypeptide ATGTGGCTGCAGAGCCTGCTGCTCTTGGGCACTGTGGCCTGCAGCATCTCTGCAC CCGCCCGCTCGCCCAGCCCCAGCACGCAGCCCTGGGAGCATGTGAATGCCATCC AGGAGGCCCGGCGTCTCCTGAACCTGAGTAGAGACACTGCTGCTGAGATGAATG AAACAGTAGAAGTCATCTCAGAAATGTTTGACCTCCAGGAGCCGACCTGCCTAC AGACCCGCCTGGAGCTGTACAAGCAGGGCCTGCGGGGCAGCCTCACCAAGCTCA AGGGCCCCTTGACCATGATGGCCAGCCACTACAAGCAGCACTGCCCTCCAACCC CGGAAACTTCCTGTGCAACCCAGATTATCACCTTTGAAAGTTTCAAAGAGAACCT GAAGGACTTTCTGCTTGTCATCCCCTTTGACTGCTGGGAGCCAGTCCAGGAGTTG CCAACTTTCTTGTACAAAGTGGTTGGCTCCACCAGCGGCAGCGGCAAGCCAGGC TCCGGCGAAGGCAGCACCAAAGGC (SEQ ID NO:66) nucleic acid encoding an exemplary Gal-9 polypeptide GCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGGA CTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCT CAGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAAT GACATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCA ACACGAGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCT TTCCAGAAGGGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCA AGGTGATGGTGAACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCA CCGTGTGGACACCATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTC CAGCCTCCCGGCGTGTGGCCTGCCAACCCGGCTCCCATTACCCAGACAGTCATCC ACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCTACTCCCGCCATCCCACCTAT GATGTACCCCCACCCCGCCTATCCGATGCCTTTCATCACCACCATTCTGGGAGGG CTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAGA GGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTCCACCTGAACCCCCG TTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAACTCCTGGGGGTCT GAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAGAGCTTCTCA GTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGTCAGCACC TGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTGGAAG TGGGGGGCGACATCCAGCTGACCCATGTGCAGACATAG (SEQ ID NO:67) nucleic acid encoding an exemplary PD1 polypeptide ATGCAGATCCCACAGGCGCCCTGGCCAGTCGTCTGGGCGGTGCTACAACTGGGC TGGCGGCCAGGATGGTTCTTAGACTCCCCAGACAGGCCCTGGAACCCCCCCACC TTCTCCCCAGCCCTGCTCGTGGTGACCGAAGGGGACAACGCCACCTTCACCTGCA GCTTCTCCAACACATCGGAGAGCTTCGTGCTAAACTGGTACCGCATGAGCCCCA GCAACCAGACGGACAAGCTGGCCGCTTTCCCCGAGGACCGCAGCCAGCCCGGCC AGGACTGCCGCTTCCGTGTCACACAACTGCCCAACGGGCGTGACTTCCACATGA GCGTGGTCAGGGCCCGGCGCAATGACAGCGGCACCTACCTCTGTGGGGCCATCT CCCTGGCCCCCAAGGCGCAGATCAAAGAGAGCCTGCGGGCAGAGCTCAGGGTG ACAGAGAGAAGGGCAGAAGTGCCCACAGCCCACCCCAGCCCCTCACCCAGGCC AGCCGGCCAGTTCCAAACCCTGGTGGTTGGTGTCGTGGGCGGCCTGCTGGGCAG CCTGGTGCTGCTAGTCTGGGTCCTGGCCGTCATCTGCTCCCGGGCCGCACGAGGG ACAATAGGAGCCAGGCGCACCGGCCAGCCCCTGAAGGAGGACCCCTCAGCCGTG CCTGTGTTCTCTATTGTTTATGCTTCCCTGGATTTCCAGTGGCGAGAGAAGACCCC GGAGCCCCCCGTGCCCTGTGTCCCTGAGCAGACGGAGTATGCCACCATTGTCTTT CCTAGCGGAATGGGCACCTCATCCCCCGCCCGCAGGGGCTCAGCCGACGGCCCT CGGAGTGCCCAGCCACTGAGGCCTGAGGATGGACACTGCTCTTGGCCCCTGACG CGTCTGCAGGATATCAAGCTTGCGGTACCGCGGGCCCGGGATCCACCGGTCGCC ACC (SEQ ID NO:68) nucleic acid encoding an exemplary TIM-3 polypeptide ATGTTTTCACATCTTCCCTTTGACTGTGTCCTGCTGCTGCTGCTGCTACTACTTAC AAGGTCCTCAGAAGTGGAATACAGAGCGGAGGTCGGTCAGAATGCCTATCTGCC CTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGCAAA GGAGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGG GATGTGAATTATTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGA GATGTGTCCCTGACCATAGAGAATGTGACTCTAGCAGACAGTGGGATCTACTGCT GCCGGATCCAAATCCCAGGCATAATGAATGATGAAAAATTTAACCTGAAGTTGG TCATCAAACCAGCCAAGGTCACCCCTGCACCGACTCTGCAGAGAGACTTCACTG CAGCCTTTCCAAGGATGCTTACCACCAGGGGACATGGCCCAGCAGAGACACAGA CACTGGGGAGCCTCCCTGATATAAATCTAACACAAATATCCACATTGGCCAATG AGTTACGGGACTCTAGATTGGCCAATGACTTACGGGACTCTGGAGCAACCATCA GAATAGGCATCTACATCGGAGCAGGGATCTGTGCTGGGCTGGCTCTGGCTCTTAT CTTCGGCGCTTTAATTTTCAAATGGTATTCTCATAGCAAAGAGAAGATACAGAAT TTAAGCCTCATCTCTTTGGCCAACCTCCCTCCCTCAGGATTGGCAAATGCAGTAG CAGAGGGAATTCGCTCAGAAGAAAACATCTATACCATTGAAGAGAACGTATATG AAGTGGAGGAGCCCAATGAGTATTATTGCTATGTCAGCAGCAGGCAGCAACCCT CACAACCTTTGGGTTGTCGCTTTGCAATGCCATAG (SEQ ID NO:69) nucleic acid encoding an exemplary CXCR3 polypeptide ATGGTTCTGGAAGTTTCCGACCACCAGGTGCTTAATGATGCGGAAGTTGCGGCAC TGCTGGAAAACTTTAGCTCATCCTATGACTACGGCGAGAACGAGTCAGACTCTTG CTGTACCTCCCCTCCTTGCCCCCAAGACTTTAGCTTGAATTTCGATCGGGCCTTCC TGCCCGCACTTTACTCTCTGCTGTTCCTGTTGGGACTGTTGGGCAACGGGGCCGT GGCAGCAGTACTGTTGAGTCGAAGGACTGCCCTGTCCAGTACCGATACATTTCTG CTGCACCTCGCCGTGGCTGACACACTGCTGGTTCTGACCCTGCCCCTTTGGGCAG TCGATGCAGCTGTCCAGTGGGTTTTCGGGAGTGGACTTTGTAAGGTGGCAGGGG CGCTGTTCAATATCAACTTCTACGCCGGAGCACTGCTGCTGGCTTGTATAAGCTT CGACCGATATCTGAACATTGTGCACGCCACGCAACTCTATAGAAGAGGCCCTCC AGCAAGGGTTACACTCACCTGTCTTGCAGTTTGGGGGCTGTGCTTGCTTTTCGCA TTGCCCGACTTCATTTTCCTGAGTGCTCACCATGACGAGCGGCTGAACGCCACTC ATTGTCAATACAACTTCCCTCAGGTGGGGAGAACAGCGCTGCGAGTGCTGCAGT TGGTGGCCGGATTCCTGCTGCCTTTGCTGGTGATGGCGTACTGCTACGCGCATAT TTTGGCGGTCTTGTTGGTTTCTAGAGGGCAAAGGCGGCTGAGGGCTATGCGACTG GTCGTTGTGGTGGTTGTCGCCTTCGCGCTCTGCTGGACCCCATACCACCTGGTGG TGCTGGTTGATATACTGATGGATTTGGGAGCCCTGGCGAGGAATTGCGGTAGAG AAAGCCGGGTCGACGTTGCAAAAAGCGTCACCTCAGGGCTGGGCTACATGCACT GTTGTCTGAACCCCCTTCTGTACGCATTCGTGGGGGTGAAGTTCCGGGAACGCAT GTGGATGTTGTTGCTGCGACTGGGTTGCCCTAATCAGCGCGGTCTGCAGCGACAG CCCAGTTCTTCTCGAAGGGACTCATCATGGTCCGAAACCTCAGAGGCTAGTTATT CTGGCCTC (SEQ ID NO:70) nucleic acid encoding an exemplary CXCR4 polypeptide ATGGAGGGGATATCAATCTACACATCAGATAATTACACGGAAGAGATGGGTTCC GGCGATTACGACTCTATGAAAGAGCCGTGTTTTAGAGAGGAAAACGCGAACTTT AACAAGATCTTTCTCCCCACCATCTACAGCATCATCTTTCTCACAGGCATCGTAG GGAACGGCCTGGTCATCCTGGTGATGGGATACCAAAAGAAGCTGAGGTCAATGA CCGACAAGTATAGGCTCCATCTGTCCGTGGCCGACCTCCTGTTTGTGATTACCCT GCCTTTTTGGGCAGTTGACGCTGTCGCTAATTGGTACTTCGGCAACTTCCTCTGTA AGGCAGTGCACGTTATCTACACTGTGAATCTTTATAGTTCCGTCTTGATCTTGGCC TTTATCAGTCTCGACAGGTATTTGGCGATTGTGCACGCTACCAACTCACAACGAC CTAGAAAACTCCTGGCTGAGAAGGTGGTTTACGTTGGTGTGTGGATTCCAGCTCT CCTGTTGACAATACCAGACTTCATTTTCGCTAATGTGAGCGAGGCCGATGACAGA TACATTTGTGACCGATTTTACCCAAACGATCTGTGGGTAGTGGTATTTCAGTTCC AACACATTATGGTCGGGCTGATCTTGCCCGGCATTGTCATACTGTCTTGCTACTG CATCATTATTTCTAAGCTGTCACACTCAAAAGGCCACCAAAAGAGGAAGGCTCT GAAAACAACGGTGATCCTGATACTGGCCTTCTTCGCATGTTGGCTGCCCTACTAT ATCGGCATCAGCATTGACTCATTTATACTCCTGGAAATTATCAAGCAGGGCTGCG AGTTCGAGAACACCGTTCATAAGTGGATTTCTATAACCGAGGCCCTCGCCTTCTT TCACTGTTGTTTGAATCCGATTCTCTACGCGTTTCTTGGCGCCAAATTTAAAACAA GCGCCCAACATGCACTGACATCAGTGTCTAGGGGGAGCTCTCTGAAAATCCTCTC CAAGGGAAAACGAGGCGGACATAGCAGTGTCAGCACTGAGTCCGAATCCAGCTC ATTTCATAGCTCT (SEQ ID NO:71) nucleic acid encoding an exemplary CTLA4 polypeptide ATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGG ACCTGGCCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGC AATGCACGTGGCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAG CTTTGTGTGTGAGTATGCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTG CTTCGGCAGGCTGACAGCCAGGTGACTGAAGTCTGTGCGGCAACCTACATGATG GGGAATGAGTTGACCTTCCTAGATGATTCCATCTGCACGGGCACCTCCAGTGGAA ATCAAGTGAACCTCACTATCCAAGGACTGAGGGCCATGGACACGGGACTCTACA TCTGCAAGGTGGAGCTCATGTACCCACCGCCATACTACCTGGGCATAGGCAACG GAACCCAGATTTATGTAATTGATCCAGAACCGTGCCCAGATTCTGACTTCCTCC TCTGGATCCTTGCAGCAGTTAGTTCGGGGTTGTTTTTTTATAGCTTTCTCCTCACA GCTGTTTCTTTGAGCAAAATGCTAAAGAAAAGAAGCCCTCTTACAACAGGGGTC TATGTGAAAATGCCCCCAACAGAGCCAGAATGTGAAAAGCAATTTCAGCCTTAT TTTATTCCCATCAATTGA (SEQ ID NO:116) nucleic acid encoding an exemplary TLR3 polypeptide ATGAGACAGACTTTGCCTTGTATCTACTTTTGGGGGGGCCTTTTGCCCTTTGGGAT GCTGTGTGCATCCTCCACCACCAAGTGCACTGTTAGCCATGAAGTTGCTGACTGC AGCCACCTGAAGTTGACTCAGGTACCCGATGATCTACCCACAAACATAACAGTG TTGAACCTTACCCATAATCAACTCAGAAGATTACCAGCCGCCAACTTCACAAGGT ATAGCCAGCTAACTAGCTTGGATGTAGGATTTAACACCATCTCAAAACTGGAGC CAGAATTGTGCCAGAAACTTCCCATGTTAAAAGTTTTGAACCTCCAGCACAATGA GCTATCTCAACTTTCTGATAAAACCTTTGCCTTCTGCACGAATTTGACTGAACTCC ATCTCATGTCCAACTCAATCCAGAAAATTAAAAATAATCCCTTTGTCAAGCAGAA GAATTTAATCACATTAGATCTGTCTCATAATGGCTTGTCATCTACAAAATTAGGA ACTCAGGTTCAGCTGGAAAATCTCCAAGAGCTTCTATTATCAAACAATAAAATTC AAGCGCTAAAAAGTGAAGAACTGGATATCTTTGCCAATTCATCTTTAAAAAAATT 105 GGAAGATTATTTGGCCTCTTTCTGAACAATGTCCAGCTGGGTCCCAGCCTTACAG AGAAGCTATGTTTGGAATTAGCAAACACAAGCATTCGGAATCTGTCTCTGAGTA ACAGCCAGCTGTCCACCACCAGCAATACAACTTTCTTGGGACTAAAGTGGACAA ATCTCACTATGCTCGATCTTTCCTACAACAACTTAAATGTGGTTGGTAACGATTC CTTTGCTTGGCTTCCACAACTAGAATATTTCTTCCTAGAGTATAATAATATACAG CATTTGTTTTCTCACTCTTTGCACGGGCTTTTCAATGTGAGGTACCTGAATTTGAA ACGGTCTTTTACTAAACAAAGTATTTCCCTTGCCTCACTCCCCAAGATTGATGATT TTTCTTTTCAGTGGCTAAAATGTTTGGAGCACCTTAACATGGAAGATAATGATAT TCCAGGCATAAAAAGCAATATGTTCACAGGATTGATAAACCTGAAATACTTAAG TCTATCCAACTCCTTTACAAGTTTGCGAACTTTGACAAATGAAACATTTGTATCA CTTGCTCATTCTCCCTTACACATACTCAACCTAACCAAGAATAAAATCTCAAAAA TAGAGAGTGATGCTTTCTCTTGGTTGGGCCACCTAGAAGTACTTGACCTGGGCCT TAATGAAATTGGGCAAGAACTCACAGGCCAGGAATGGAGAGGTCTAGAAAATAT TTTCGAAATCTATCTTTCCTACAACAAGTACCTGCAGCTGACTAGGAACTCCTTT GCCTTGGTCCCAAGCCTTCAACGACTGATGCTCCGAAGGGTGGCCCTTAAAAAT GTGGATAGCTCTCCTTCACCATTCCAGCCTCTTCGTAACTTGACCATTCTGGATCT AAGCAACAACAACATAGCCAACATAAATGATGACATGTTGGAGGGTCTTGAGAA ACTAGAAATTCTCGATTTGCAGCATAACAACTTAGCACGGCTCTGGAAACACGC AAACCCTGGTGGTCCCATTTATTTCCTAAAGGGTCTGTCTCACCTCCACATCCTTA ACTTGGAGTCCAACGGCTTTGACGAGATCCCAGTTGAGGTCTTCAAGGATTTATT TGAACTAAAGATCATCGATTTAGGATTGAATAATTTAAACACACTTCCAGCATCT GTCTTTAATAATCAGGTGTCTCTAAAGTCATTGAACCTTCAGAAGAATCTCATAA CATCCGTTGAGAAGAAGGTTTTCGGGCCAGCTTTCAGGAACCTGACTGAGTTAG ATATGCGCTTTAATCCCTTTGATTGCACGTGTGAAAGTATTGCCTGGTTTGTTAAT TGGATTAACGAGACCCATACCAACATCCCTGAGCTGTCAAGCCACTACCTTTGCA ACACTCCACCTCACTATCATGGGTTCCCAGTGAGACTTTTTGATACATCATCTTGC AAAGACAGTGCCCCCTTTGAACTCTTTTTCATGATCAATACCAGTATCCTGTTGA TTTTTATCTTTATTGTACTTCTCATCCACTTTGAGGGCTGGAGGATATCTTTTTATT GGAATGTTTCAGTACATCGAGTTCTTGGTTTCAAAGAAATAGACAGACAGACAG AACAGTTTGAATATGCAGCATATATAATTCATGCCTATAAAGATAAGGATTGGGT CTGGGAACATTTCTCTTCAATGGAAAAGGAAGACCAATCTCTCAAATTTTGTCTG GAAGAAAGGGACTTTGAGGCGGGTGTTTTTGAACTAGAAGCAATTGTTAACAGC ATCAAAAGAAGCAGAAAAATTATTTTTGTTATAACACACCATCTATTAAAAGAC CCATTATGCAAAAGATTCAAGGTACATCATGCAGTTCAACAAGCTATTGAACAA AATCTGGATTCCATTATATTGGTTTTCCTTGAGGAGATTCCAGATTATAAACTGA ACCATGCACTCTGTTTGCGAAGAGGAATGTTTAAATCTCACTGCATCTTGAACTG GCCAGTTCAGAAAGAACGGATAGGTGCCTTTCGTCATAAATTGCAAGTAGCACT TGGATCCAAAAACTCTGTACATTAA (SEQ ID NO:117) nucleic acid encoding an exemplary TLR4 polypeptide ATGATGTCTGCCTCGCGCCTGGCTGGGACTCTGATCCCAGCCATGGCCTTCCTCT CCTGCGTGAGACCAGAAAGCTGGGAGCCCTGCGTGGAGGTGGTTCCTAATATTA CTTATCAATGCATGGAGCTGAATTTCTACAAAATCCCCGACAACCTCCCCTTCTC AACCAAGAACCTGGACCTGAGCTTTAATCCCCTGAGGCATTTAGGCAGCTATAG CTTCTTCAGTTTCCCAGAACTGCAGGTGCTGGATTTATCCAGGTGTGAAATCCAG ACAATTGAAGATGGGGCATATCAGAGCCTAAGCCACCTCTCTACCTTAATATTGA CAGGAAACCCCATCCAGAGTTTAGCCCTGGGAGCCTTTTCTGGACTATCAAGTTT ACAGAAGCTGGTGGCTGTGGAGACAAATCTAGCATCTCTAGAGAACTTCCCCAT TGGACATCTCAAAACTTTGAAAGAACTTAATGTGGCTCACAATCTTATCCAATCT TTCAAATTACCTGAGTATTTTTCTAATCTGACCAATCTAGAGCACTTGGACCTTTC CAGCAACAAGATTCAAAGTATTTATTGCACAGACTTGCGGGTTCTACATCAAATG CCCCTACTCAATCTCTCTTTAGACCTGTCCCTGAACCCTATGAACTTTATCCAACC AGGTGCATTTAAAGAAATTAGGCTTCATAAGCTGACTTTAAGAAATAATTTTGAT AGTTTAAATGTAATGAAAACTTGTATTCAAGGTCTGGCTGGTTTAGAAGTCCATC GTTTGGTTCTGGGAGAATTTAGAAATGAAGGAAACTTGGAAAAGTTTGACAAAT CTGCTCTAGAGGGCCTGTGCAATTTGACCATTGAAGAATTCCGATTAGCATACTT AGACTACTACCTCGATGATATTATTGACTTATTTAATTGTTTGACAAATGTTTCTT CATTTTCCCTGGTGAGTGTGACTATTGAAAGGGTAAAAGACTTTTCTTATAATTT CGGATGGCAACATTTAGAATTAGTTAACTGTAAATTTGGACAGTTTCCCACATTG AAACTCAAATCTCTCAAAAGGCTTACTTTCACTTCCAACAAAGGTGGGAATGCTT TTTCAGAAGTTGATCTACCAAGCCTTGAGTTTCTAGATCTCAGTAGAAATGGCTT GAGTTTCAAAGGTTGCTGTTCTCAAAGTGATTTTGGGACAACCAGCCTAAAGTAT TTAGATCTGAGCTTCAATGGTGTTATTACCATGAGTTCAAACTTCTTGGGCTTAG AACAACTAGAACATCTGGATTTCCAGCATTCCAATTTGAAACAAATGAGTGAGTT TTCAGTATTCCTATCACTCAGAAACCTCATTTACCTTGACATTTCTCATACTCACA CCAGAGTTGCTTTCAATGGCATCTTCAATGGCTTGTCCAGTCTCGAAGTCTTGAA AATGGCTGGCAATTCTTTCCAGGAAAACTTCCTTCCAGATATCTTCACAGAGCTG AGAAACTTGACCTTCCTGGACCTCTCTCAGTGTCAACTGGAGCAGTTGTCTCCAA CAGCATTTAACTCACTCTCCAGTCTTCAGGTACTAAATATGAGCCACAACAACTT CTTTTCATTGGATACGTTTCCTTATAAGTGTCTGAACTCCCTCCAGGTTCTTGATT ACAGTCTCAATCACATAATGACTTCCAAAAAACAGGAACTACAGCATTTTCCAA GTAGTCTAGCTTTCTTAAATCTTACTCAGAATGACTTTGCTTGTACTTGTGAACAC CAGAGTTTCCTGCAATGGATCAAGGACCAGAGGCAGCTCTTGGTGGAAGTTGAA CGAATGGAATGTGCAACACCTTCAGATAAGCAGGGCATGCCTGTGCTGAGTTTG AATATCACCTGTCAGATGAATAAGACCATCATTGGTGTGTCGGTCCTCAGTGTGC TTGTAGTATCTGTTGTAGCAGTTCTGGTCTATAAGTTCTATTTTCACCTGATGCTT CTTGCTGGCTGCATAAAGTATGGTAGAGGTGAAAACATCTATGATGCCTTTGTTA TCTACTCAAGCCAGGATGAGGACTGGGTAAGGAATGAGCTAGTAAAGAATTTAG AAGAAGGGGTGCCTCCATTTCAGCTCTGCCTTCACTACAGAGACTTTATTCCCGG TGTGGCCATTGCTGCCAACATCATCCATGAAGGTTTCCATAAAAGCCGAAAGGT GATTGTTGTGGTGTCCCAGCACTTCATCCAGAGCCGCTGGTGTATCTTTGAATAT GAGATTGCTCAGACCTGGCAGTTTCTGAGCAGTCGTGCTGGTATCATCTTCATTG TCCTGCAGAAGGTGGAGAAGACCCTGCTCAGGCAGCAGGTGGAGCTGTACCGCC TTCTCAGCAGGAACACTTACCTGGAGTGGGAGGACAGTGTCCTGGGGCGGCACA TCTTCTGGAGACGACTCAGAAAAGCCCTGCTGGATGGTAAATCATGGAATCCAG AAGGAACAGTGGGTACAGGATGCAATTGGCAGGAAGCAACATCTATCTGA (SEQ ID NO:118) nucleic acid encoding an exemplary TLR9 polypeptide ATGGGTTTCTGCCGCAGCGCCCTGCACCCGCTGTCTCTCCTGGTGCAGGCCATCA TGCTGGCCATGACCCTGGCCCTGGGTACCTTGCCTGCCTTCCTACCCTGTGAGCT CCAGCCCCACGGCCTGGTGAACTGCAACTGGCTGTTCCTGAAGTCTGTGCCCCAC TTCTCCATGGCAGCACCCCGTGGCAATGTCACCAGCCTTTCCTTGTCCTCCAACC GCATCCACCACCTCCATGATTCTGACTTTGCCCACCTGCCCAGCCTGCGGCATCT CAACCTCAAGTGGAACTGCCCGCCGGTTGGCCTCAGCCCCATGCACTTCCCCTGC CACATGACCATCGAGCCCAGCACCTTCTTGGCTGTGCCCACCCTGGAAGAGCTA AACCTGAGCTACAACAACATCATGACTGTGCCTGCGCTGCCCAAATCCCTCATAT CCCTGTCCCTCAGCCATACCAACATCCTGATGCTAGACTCTGCCAGCCTCGCCGG CCTGCATGCCCTGCGCTTCCTATTCATGGACGGCAACTGTTATTACAAGAACCCC TGCAGGCAGGCACTGGAGGTGGCCCCGGGTGCCCTCCTTGGCCTGGGCAACCTC ACCCACCTGTCACTCAAGTACAACAACCTCACTGTGGTGCCCCGCAACCTGCCTT CCAGCCTGGAGTATCTGCTGTTGTCCTACAACCGCATCGTCAAACTGGCGCCTGA GGACCTGGCCAATCTGACCGCCCTGCGTGTGCTCGATGTGGGCGGAAATTGCCG CCGCTGCGACCACGCTCCCAACCCCTGCATGGAGTGCCCTCGTCACTTCCCCCAG CTACATCCCGATACCTTCAGCCACCTGAGCCGTCTTGAAGGCCTGGTGTTGAAGG ACAGTTCTCTCTCCTGGCTGAATGCCAGTTGGTTCCGTGGGCTGGGAAACCTCCG AGTGCTGGACCTGAGTGAGAACTTCCTCTACAAATGCATCACTAAAACCAAGGC CTTCCAGGGCCTAACACAGCTGCGCAAGCTTAACCTGTCCTTCAATTACCAAAAG AGGGTGTCCTTTGCCCACCTGTCTCTGGCCCCTTCCTTCGGGAGCCTGGTCGCCCT GAAGGAGCTGGACATGCACGGCATCTTCTTCCGCTCACTCGATGAGACCACGCT CCGGCCACTGGCCCGCCTGCCCATGCTCCAGACTCTGCGTCTGCAGATGAACTTC ATCAACCAGGCCCAGCTCGGCATCTTCAGGGCCTTCCCTGGCCTGCGCTACGTGG ACCTGTCGGACAACCGCATCAGCGGAGCTTCGGAGCTGACAGCCACCATGGGGG AGGCAGATGGAGGGGAGAAGGTCTGGCTGCAGCCTGGGGACCTTGCTCCGGCCC CAGTGGACACTCCCAGCTCTGAAGACTTCAGGCCCAACTGCAGCACCCTCAACTT CACCTTGGATCTGTCACGGAACAACCTGGTGACCGTGCAGCCGGAGATGTTTGC CCAGCTCTCGCACCTGCAGTGCCTGCGCCTGAGCCACAACTGCATCTCGCAGGCA GTCAATGGCTCCCAGTTCCTGCCGCTGACCGGTCTGCAGGTGCTAGACCTGTCCC ACAATAAGCTGGACCTCTACCACGAGCACTCATTCACGGAGCTACCGCGACTGG AGGCCCTGGACCTCAGCTACAACAGCCAGCCCTTTGGCATGCAGGGCGTGGGCC ACAACTTCAGCTTCGTGGCTCACCTGCGCACCCTGCGCCACCTCAGCCTGGCCCA CAACAACATCCACAGCCAAGTGTCCCAGCAGCTCTGCAGTACGTCGCTGCGGGC CCTGGACTTCAGCGGCAATGCACTGGGCCATATGTGGGCCGAGGGAGACCTCTA TCTGCACTTCTTCCAAGGCCTGAGCGGTTTGATCTGGCTGGACTTGTCCCAGAAC CGCCTGCACACCCTCCTGCCCCAAACCCTGCGCAACCTCCCCAAGAGCCTACAG GTGCTGCGTCTCCGTGACAATTACCTGGCCTTCTTTAAGTGGTGGAGCCTCCACT TCCTGCCCAAACTGGAAGTCCTCGACCTGGCAGGAAACCAGCTGAAGGCCCTGA CCAATGGCAGCCTGCCTGCTGGCACCCGGCTCCGGAGGCTGGATGTCAGCTGCA ACAGCATCAGCTTCGTGGCCCCCGGCTTCTTTTCCAAGGCCAAGGAGCTGCGAG AGCTCAACCTTAGCGCCAACGCCCTCAAGACAGTGGACCACTCCTGGTTTGGGC CCCTGGCGAGTGCCCTGCAAATACTAGATGTAAGCGCCAACCCTCTGCACTGCG CCTGTGGGGCGGCCTTTATGGACTTCCTGCTGGAGGTGCAGGCTGCCGTGCCCGG TCTGCCCAGCCGGGTGAAGTGTGGCAGTCCGGGCCAGCTCCAGGGCCTCAGCAT CTTTGCACAGGACCTGCGCCTCTGCCTGGATGAGGCCCTCTCCTGGGACTGTTTC GCCCTCTCGCTGCTGGCTGTGGCTCTGGGCCTGGGTGTGCCCATGCTGCATCACC TCTGTGGCTGGGACCTCTGGTACTGCTTCCACCTGTGCCTGGCCTGGCTTCCCTG GCGGGGGCGGCAAAGTGGGCGAGATGAGGATGCCCTGCCCTACGATGCCTTCGT GGTCTTCGACAAAACGCAGAGCGCAGTGGCAGACTGGGTGTACAACGAGCTTCG GGGGCAGCTGGAGGAGTGCCGTGGGCGCTGGGCACTCCGCCTGTGCCTGGAGGA ACGCGACTGGCTGCCTGGCAAAACCCTCTTTGAGAACCTGTGGGCCTCGGTCTAT GGCAGCCGCAAGACGCTGTTTGTGCTGGCCCACACGGACCGGGTCAGTGGTCTC TTGCGCGCCAGCTTCCTGCTGGCCCAGCAGCGCCTGCTGGAGGACCGCAAGGAC GTCGTGGTGCTGGTGATCCTGAGCCCTGACGGCCGCCGCTCCCGCTACGTGCGGC TGCGCCAGCGCCTCTGCCGCCAGAGTGTCCTCCTCTGGCCCCACCAGCCCAGTGG TCAGCGCAGCTTCTGGGCCCAGCTGGGCATGGCCCTGACCAGGGACAACCACCA CTTCTATAACCGGAACTTCTGCCAGGGACCCACGGCCGAATAG (SEQ ID NO:119) nucleic acid encoding an exemplary TNFR2 polypeptide ATGGCGCCCGTCGCCGTCTGGGCCGCGCTGGCCGTCGGACTGGAGCTCTGGGCT GCGGCGCACGCCTTGCCCGCCCAGGTGGCATTTACACCCTACGCCCCGGAGCCC GGGAGCACATGCCGGCTCAGAGAATACTATGACCAGACAGCTCAGATGTGCTGC AGCAAATGCTCGCCGGGCCAACATGCAAAAGTCTTCTGTACCAAGACCTCGGAC ACCGTGTGTGACTCCTGTGAGGACAGCACATACACCCAGCTCTGGAACTGGGTT CCCGAGTGCTTGAGCTGTGGCTCCCGCTGTAGCTCTGACCAGGTGGAAACTCAA GCCTGCACTCGGGAACAGAACCGCATCTGCACCTGCAGGCCCGGCTGGTACTGC GCGCTGAGCAAGCAGGAGGGGTGCCGGCTGTGCGCGCCGCTGCGCAAGTGCCGC CCGGGCTTCGGCGTGGCCAGACCAGGAACTGAAACATCAGACGTGGTGTGCAAG CCCTGTGCCCCGGGGACGTTCTCCAACACGACTTCATCCACGGATATTTGCAGGC CCCACCAGATCTGTAACGTGGTGGCCATCCCTGGGAATGCAAGCATGGATGCAG TCTGCACGTCCACGTCCCCCACCCGGAGTATGGCCCCAGGGGCAGTACACTTACC CCAGCCAGTGTCCACACGATCCCAACACACGCAGCCAACTCCAGAACCCAGCAC TGCTCCAAGCACCTCCTTCCTGCTCCCAATGGGCCCCAGCCCCCCAGCTGAAGGG AGCACTGGCGACTTCGCTCTTCCAGTTGGACTGATTGTGGGTGTGACAGCCTTGG GTCTACTAATAATAGGAGTGGTGAACTGTGTCATCATGACCCAGGTGAAAAAGA AGCCCTTGTGCCTGCAGAGAGAAGCCAAGGTGCCTCACTTGCCTGCCGATAAGG CCCGGGGTACACAGGGCCCCGAGCAGCAGCACCTGCTGATCACAGCGCCGAGCT CCAGCAGCAGCTCCCTGGAGAGCTCGGCCAGTGCGTTGGACAGAAGGGCGCCCA CTCGGAACCAGCCACAGGCACCAGGCGTGGAGGCCAGTGGGGCCGGGGAGGCC CGGGCCAGCACCGGGAGCTCAGATTCTTCCCCTGGTGGCCATGGGACCCAGGTC AATGTCACCTGCATCGTGAACGTCTGTAGCAGCTCTGACCACAGCTCACAGTGCT CCTCCCAAGCCAGCTCCACAATGGGAGACACAGATTCCAGCCCCTCGGAGTCCC CGAAGGACGAGCAGGTCCCCTTCTCCAAGGAGGAATGTGCCTTTCGGTCACAGC TGGAGACGCCAGAGACCCTGCTGGGGAGCACCGAAGAGAAGCCCCTGCCCCTTG GAGTGCCTGATGCTGGGATGAAGCCCAGTTAA (SEQ ID NO:120) Example 4: Bioengineering Mesenchymal Stromal Cells with Chimeric Antigen Receptors for Enhanced Immunosuppressive Treatment Efficacy This Example describes the design and engineering of MSCs to express one or more chimeric antigen receptors (CARs-MSCs) and describes how such CAR-MSCs can enhance immunosuppression at antigen-specific inflammatory target sites. The results in this Example re-present and expand on at least some of the results provided in other Examples. Methods Cell Lines, Primary Peripheral Blood Mononuclear Cells (PBMCs), Primary T cells, and Primary Mesenchymal Stromal Cells (MSCs) Primary human adipose-derived MSCs were obtained and cultured with StemXVivo Mesenchymal Stem Cell Expansion Media (R&D Systems, Minneapolis, MN). Human embryonic kidney 293 (HEK-293T) and human epithelial breast cancer cell line (MCF7) were obtained from ATCC (HTB-22, Manassas, VA, USA) and cultured in D10 (DMEM Gibco, Gaithersburg, MD, US) with 10% (v/v) fetal bovine serum (FBS, Millipore Sigma, Ontario, Canada) and 1% (v/v) penicillin-streptomycin-glutamine (PSG, Gibco, Gaithersburg, MD, US). HEK-293T were used for lentiviral production. MCF7 was irradiated and confirmed for E-cadherin (Ecad) positivity by flow cytometry for use as a form of CAR-based single chain variable fragment (scFv) stimulation within in vivo tumor models as described. Normal Human Primary Epidermal Keratinocytes were derived from the epidermis of juvenile or adult foreskin from single or pooled donors and cultured in Keratinocyte growth media (PromoCell, Heidelberg, Germany). Normal Human Primary Bronchial Epithelial Cells were isolated from the epithelial lining of airways above bifurcation of the lungs (Lonza, Cohasset, MN). These cells were subsequently cultured in Airway epithelial cell basal medium expansion media (PromoCell, Heidelberg, Germany). Acute lymphoblastic leukemia cell line NALM6 and mantle cell lymphoma cell line JeKo-1 were also purchased from ATCC (CRL-3273 and CRL-3006, respectively, Manassas, MD, US) with 20% (v/v) or 10% (v/v) FBS (Millipore Sigma, Ontario, Canada), respectively, and 1% (v/v) PSG (Gibco, Gaithersburg, MD, US). For in vivo experiment use, cell lines were transduced with luciferase-ZsGreen lentivirus (Addgene, Cambridge, MA, USA). In addition, NALM6 and/ or luciferase ⁺ NALM6 were transduced with human Ecad- encoding lentivirus as a form of cell-based Ecad stimulation (GeneCopoeia, Rockville, MD). Cell lines were cultured up to 20 passages, and fresh aliquots were thawed every 7–8 weeks. Cell lines were authenticated by the manufacturer and routinely checked for phenotype by flow cytometry. Cell lines were tested monthly for mycoplasma. PBMCs were isolated from de-identified normal donor blood apheresis cones using SepMate tubes (STEMCELL Technologies, Vancouver, Canada). T cells were separated with negative selection magnetic beads using EasySepTM Human T Cell 80 Isolation Kit (STEMCELL Technologies, Vancouver, Canada). Primary T cells and PBMCs were cultured in T cell medium containing X-VIVO 15 (Lonza, Walkersville, MD, USA), 10% (v/v) human serum albumin (Innovative Research, Novi, MI, USA), and 1% (v/v) PSG (Gibco, Gaithersburg, MD, USA) before selection for in vitro coculture. Freshly isolated human PBMCs were injected via i.v. administration for in vivo experiments. scFv Phage Display Library hmcECAD.6 scFv sequence was generated and optimized for binding to Ecad protein through phage display library selection. A naive human scFv library of approximately 2x10 ⁹ diversity was used to screen against recombinant Ecad protein (Biomolecular Discovery, Rochester, NY). The hmcECAD.6 scFv clone was identified after two rounds of screening against mouse Ecad followed by another round of panning on human Ecad Fc chimeric protein (both from BioLegend, San Diego, CA). This clone was shown to react with mouse Ecad by phage ELISA. Relative affinity versus the FLAG antibody estimated the hmcECAD.6 clone to be approximately 5 nM. Final hmcECAD.6 sequence (SEQ ID NO: 90) was codon optimized for cloning of heavy and light chain into EcCAR plasmid. Chimeric Antigen Receptor (CAR) Design and Virus Production MSCs were transduced via lentiviral vectors encoding specifically designed CAR constructs under EF-1 alpha promoter. Optimization of transduction was performed with CD19-targeted CAR (CAR19) construct. See, for example, June et al., Science 359, 1361- 1365 (2018). CAR19 is composed of a CD19-directed scFv derived from clone FMC-63 and fused to 4-1BB and CD3 ζ signaling domains (FMC63-41BB-?). A VSV-g-pseudotyped second-generation lentivirus loaded with CAR transgene was generated via lipofectamine transfection of HEK-293T cells, followed by standard procedures for harvesting, concentration, and functional titration of lentivirus. See, for example, Sterneret al. Blood 133, 697-709 (2019) and Sakemura et al. Blood 139(26):3708-3721 (2022). CAR constructs were designed to include an scFv against human/canine Ecad (Figure 23A) with CD28ζ intracellular signaling domain to induce MSC immunomodulatory activation (Figure 23B). CAR plasmid was generated and sequence validated. Pre-seeded MSCs (concentration of 250,000 cells/well) were transduced in a 6-well plate with lentiviral particles at a multiplicity of infection (MOI) of 3 with various concentrations of protamine sulfate (25, 50, 100 ug/uL) for optimization of CAR expression and MSC proliferation. T Cell Suppression Assay To test the ability of CAR-MSCs to inhibit activated T cells, a T cell suppression assay was used. Briefly, untransduced (UTD)-MSCs or EcCAR-MSCs (suppressors) were co-cultured with activated T cells (effectors) in the presence or absence of 1) soluble Ecad (stimulator) or 2) a matched Ecad ⁺ and Ecad- NALM6 cell line to provide both soluble and cell-based antigen-specific stimulation to the CAR-MSCs. T cells were isolated from PBMCs of normal donors using negative selection magnetic beads. See, for example, Sterner et al. Blood 133, 697-709 (2019). Isolated T cells were non-specifically activated using CD3/CD28 stimulating beads (Dynabeads, Invitrogen, Waltham, MA, USA) at a 1:1 bead to T cell ratio in T cell medium containing X-VIVO 15 (Lonza, Walkersville, MD, USA), 10% (v/v) human serum albumin (Innovative Research, Novi, MI, USA), and 1% (v/v) PSG (Gibco, Gaithersburg, MD, USA). MSCs were preincubated with or without soluble Ecad protein (250ng-1000ng/mL) or matched Ecad ⁺ and Ecad- cell lines (1:1 MSC to Ecad ⁺ cell ratio) (stimulator) to activate EcCAR-MSCs specifically through the CAR in StemXVivo serum- free Mesenchymal Stem Cell Expansion media (R&D Systems, Minneapolis, MN, USA). After 24 hours, stimulated T cells (effectors) were co-cultured with UTD-MSCs or EcCAR- MSCs (suppressors). Cells were co-cultured at a 1:5 MSC to T cell ratio with 250,000 T cells per 6-well plate. Cells were harvested and analyzed by flow cytometry after different coculture time points as indicated in individual experiments. Multiparametric Flow Cytometry Staining for flow cytometry was performed. Briefly, MSCs were isolated and grown in culture, then transduced with CAR to create CAR-MSCs to be cocultured with T cells / PBMCs in 96-well plates for 24-hour assays and 6-well plates for longer culture. Following desired coculture durations, adherent MSCs were detached with Accutase (STEMCELL Technologies, Vancouver, Canada) at 10 mL per 75 cm ² surface area and incubated for 10-15 minutes at 37°C. Following detachment, all well contents were spun and washed in flow buffer (Phosphate-buffered saline (PBS), 2% (v/v) FBS, and 1% (v/v) sodium azide) and stained with desired antibodies for 15 minutes in the dark at room temperature. Following final wash steps, cells were analyzed for desired surface markers, and positivity was determined through negative gating by fluorescence minus one (FMO) control wells. Absolute cell count numbers were obtained using volumetric measurement. Cells were gated on SSC vs. FSC plots for cell separation by size and complexity, FSC-H vs. FSC-A plots to exclude doublets, and live/dead Aqua staining (Cat#L34966, Thermo Fisher Scientific, Waltham, MA, USA) to exclude dead cells, followed by cell subset characterization based on predesigned antibody panels which were optimized and used to stain samples. Anti-human antibodies were purchased from Biolegend, eBioscience, or BD Biosciences (San Diego, CA, USA). Samples were prepared for flow cytometry. See, for example, Sakemura et al. Blood 139(26):3708-3721 (2022). All antibodies used to stain are listed in (Table 4). Flow cytometry was performed on three-laser CytoFLEX (Beckman Coulter, Chaska, MN, USA) where cells were gated by singlet discrimination and live cells were determined by live/dead aqua staining (Cat#L34966, Thermo Fisher Scientific, Waltham, MA, USA). All gating analyses were performed with FlowJo X10.0.7r2 software (Becton Dickenson, Ashland, OR, USA) or Kaluza Analysis software (Beckman Coulter, Indianapolis, Indiana, USA). Table 4. List of antibodies used for flow cytometry, clone, vendor, and catalog numbers. In Vivo Mouse Studies Female and male immunocompromised NOD-SCID-? ^-/- (NSG) mice were obtained from Jackson Laboratories at 6-8 weeks old and housed in BSL2+ animal facilities. All cells were injected in 100-200 uL of PBS via syringe through tail vein i.v. or i.p. injection. Mice were imaged with bioluminescent imaging (BLI) using an IVIS® Lumina S5 Imaging System (PerkinElmer, Hopkinton, MA, USA) to confirm engraftment of luciferase ⁺ CD19 ⁺ NALM6/ JeKo-1 cells in the cancer xenograft model or luciferase ⁺ CAR-MSCs in the MSC persistence xenograft model. Imaging was performed 10?minutes after the i.p. injection of 10?µL/g D-luciferin (15?mg/mL, Gold Biotechnology, St. Louis, MO, USA). In Ecad tumor xenograft models, NSG mice were engrafted with Ecad ⁺ or Ecad- luciferase ⁺ CD19 ⁺ NALM6 (1 x 10 ⁶ cells given i.v.). Engraftment was confirmed by BLI 5 days after injection, and mice were randomized to receive either UTD-MSCs or EcCAR-MSCs (1 x 10 ⁶ cells given i.p.) along with CD19-targeted CART cells (CART19) (1 x 10 ⁶ cells given i.v. as a strategy to treat the CD19 ⁺ tumor) (Figure 17A). Upon efficient CART19 killing of NALM6 tumor burden, mice were rechallenged to again receive Ecad ⁺ or Ecad- luciferase ⁺ CD19 ⁺ NALM6 (1 x 10 ⁶ cells given i.v.) and UTD-MSCs or EcCAR-MSCs (1 x 10 ⁶ cells given i.p.). Serial BLI was subsequently performed to assess residual disease and determine antitumor activity of CART19 cells on Ecad ⁺ NALM6 and Ecad- NALM6. In supplementary tumor models, NSG mice were engrafted with luciferase ⁺ CD19 ⁺ JeKo-1 or NALM6 (1 x 10 ⁶ cells given i.v.). Engraftment was confirmed by BLI 1-2 weeks or 5 days after injection depending on tumor subtype. All mice then received irradiated Ecad ⁺ MCF7 cells (5 x 10 ⁶ cells given i.p. to stimulate the EcCAR-MSCs) and CART19 (1 x 10 ⁶ cells given i.v. as a strategy to treat the CD19 ⁺ tumor). Mice were then randomized based on BLI as a measure of tumor burden to receive UTD-MSCs, EcCAR-MSCs, or no additional treatment (Figure 25B). Serial BLI was subsequently performed to assess residual disease and determine antitumor activity of CART19 cells. In Graft vs. Host disease (GVHD) models, GVHD was induced in NSG mice with allogeneic human PBMCs (20-30 x 10 ⁶ cells i.v.) and treated with UTD-MSCs (1 x 10 ⁶ cells i.p. every 3 weeks) or EcCAR-MSCs (1 x 10 ⁶ cells i.p. every 3 weeks) (Figures 17D-17G). Body weight and clinical GVHD scoring (based on body weight, posture, diarrhea, activity, fur condition, and skin integrity, Table 5) were monitored in all experiments for GVHD progression in each experimental group. Table 5. GVHD clinical scoring system. In acute GVHD models, GVHD was more rapidly induced in NSG mice by first irradiating the mice at a dose of 250cGy. Allogeneic human PBMCs (10-15 x 10 ⁶ cells i.v.) were then given to irradiated mice, and groups were subsequently randomized by weight to receive UTD- or CAR-MSCs (Figure 18A). Luciferase ⁺ GFP ⁺ CD19-CAR-MSCs were utilized as a control for luciferase ⁺ GFP ⁺ EcCAR-MSC treatment. MSC localization was detected in the organs by BLI and immunofluorescent staining. Allogeneic PBMCs were B- cell depleted using CD19 Pan B Cell Dynabeads (Invitrogen, Waltham, MA, USA) to ensure no human CD19 ⁺ cells were present in the mice to stimulate CD19CAR-MSCs. Body weight and clinical GVHD scoring were monitored in all experiments for GVHD progression in each experimental group with the same criteria as listed (above). To assess trafficking and localization of luciferase ⁺ anti-Ecad CAR-MSCs and luciferase ⁺ anti-CD19 CAR-MSC, mice were also imaged with bioluminescent imaging (BLI) using an IVIS® Lumina S5 Imaging System (PerkinElmer, Hopkinton, MA, USA). One week following MSCs injection in acute GVHD xenograft models, satellite mice were randomly selected for euthanasia and subsequent organ flux assessment. Here, organ imaging was performed 10-20?minutes after a 250uL i.p. injection of 50mg/mL D-luciferin (Gold Biotechnology, St. Louis, MO, USA) to detect luciferase ⁺ MSCs in the colon, kidneys, liver, lung and spleen relative to whole body BLI detection. For all in vivo experiments, mouse blood was collected by tail vein bleeding (approximately 100 µL), with 70 µL of blood used for flow cytometry analysis. Red blood cell (RBC) lysis was applied using 1:10 BD FACS Lyse buffer (BD Biosciences, San Jose, CA, USA). Cells were then washed in flow buffer and incubated with their specific antibody mix at room temperature in the dark before flow analysis using CytoFLEX (Beckman Coulter, Chaska, MN, USA) was performed. The remainder of the blood was centrifuged at 4 ^o C, 13,000 rpm for 10 minutes to separate serum for cytokine analysis. Immunofluorescent Staining In the acute GVHD mouse xenograft model, satellite mice were sacrificed, and organs were harvested and preserved, including colon, liver, lungs, and heart 7 days following MSC injection. Organs were fixed in 4% paraformaldehyde for 48 hours and promptly frozen in Tissue-Tek O.C.T Compound (Sakura, Hayward, CA) for frozen sectioning and slide preparation. Tissue slides were next thawed from -80 ^o C storage and washed in PBS, slides were incubated 0.1% Sudan Black (Sigma-Aldrich, Burlington, MA) solution and solubilized in blocking buffer containing 0.3% Triton-X-100 (Thermo Fisher Scientific, Waltham, MA, USA) and 5% bovine serum albumin (Sigma-Aldrich, Burlington, MA). Antigen retrieval was performed through boiling in unmasking solution for 15 minutes. Tissues were incubated with primary antibodies for 1 hour at room temperature to stain for Ecad (cat.144725, Cell Signaling Technology, Danvers, MA) and GFP ⁺ CAR-MSCs (cat. Ab183734, Abcam, Boston, MA). Secondary antibodies (cat. A11001, cat. A11012, Thermo Fisher Scientific, Waltham, MA, USA) were next incubated over slides for 1 hour at room temperature. Slides were imaged on a Zeiss LSM 980 Confocal Microscope (Zeiss Group, Oberkochen, Germany) and analyzed using ZEN 2.3 Microscopy Software (Zeiss Group, Oberkochen, Germany). MSC localization to Ecad ⁺ colonic crypts were compared across EcCAR-MSC, CD19CAR-MSC, and no MSCs (negative control) groups. Localization was calculated by quantification of colonic crypts containing GFP ⁺ MSCs over an average of five 40x magnified microscopic fields across each condition (Figures 18F-18G and Figures 21D and 21F). Canine Studies Ecad-targeted CAR expressed on human MSCs in all experiments was based on a human/mouse/canine cross-reactive scFv. This scFv was generated using phage display, and cross-reactivity with both dog and human Ecad was confirmed (Figure 23A-23D). EcCAR- MSCs in healthy beagles. Subjects were injected i.p. with EcCAR-MSCs (2 x 10 ⁶ cells/kg). Subjects were followed daily, weights were monitored, and serial blood sampling was performed. Colon biopsies were performed on Day 3 and examined by hematoxylin and eosin (H&E) to assess tissue integrity. RNA Isolation, Sequencing, and Analysis EcCAR-MSCs or UTD-MSCs were stimulated accordingly in culture with or without Recombinant Human E-cadherin Fc chimera (BioLegend, San Diego, CA, USA) at 250 ng/mL as a form of CAR specific stimulation for 24 hours. Following in vitro culture, MSCs were detached, and RNA was isolated using a QIAGEN RNeasy Plus Mini Kit (Cat#74134, QIAGEN, Germantown, MD, USA). Bulk RNA sequencing was performed on MSCs from 3 different biological donor replicates in both UTD-MSC and EcCAR-MSC groups to ensure rigor of results. Total RNA was prepped with a SMARTer stranded total RNA-seq kit v2, Pico input mammalian (Takara, Mountain View, CA, USA). Total RNA (three samples per lane) was sequenced on an Illumina HiSeq 4000 (Illumina, San Diego, CA, USA). Library preparation and sequencing were performed by the Medical Genome Facility Genome Analysis Core (Mayo Clinic, Rochester, MN, USA). Quality check was performed with FastQC v0.11.8 on sample generated fastqc files. Cutadapt v1.18 was used to trim and remove adapter sequences. Output files were confirmed for adaptor removal and quality using FastQC v0.11.8. Paired end reads from trimmed fastq files were mapped to the latest human reference genome (GRCh38) downloaded from NCBI (ncbi.nlm.nih.gov/). Genome index files were built and aligned with STAR v2.5.4b. Generic expression counts for each gene were generated with HTSeq (Python 3.6.5). Gene counts were normalized (geometric mean) and differential expression analysis was calculated with DESeq2 (R v3.6.1) using adjusted p values ?0.05 as statistical cut offs. Heatmaps were created using pheatmap with PCAs generated with ggplot2 and Prism Graph Pad (La Jolla, CA,). Gene set enrichment analysis for cell phenotypes were performed using Enrichr Cell Augmented Gene set. Activated and inhibited canonical pathways, molecules, and protein-protein interaction networks were generated using Ingenuity Pathway Analysis (QIAGEN, Redwood City, CA, USA) with stringent p value and fold change cut offs (p?0.01, ±1 fold change) across differential gene expression comparisons. Multiplex Cytokine Assays Cytokine assays were performed on mouse serum samples collected 2 weeks following MSC or control treatment. In vitro cytokine assays were performed on supernatant collected 24 following coculture with MSCs and stimulation source. Debris were removed from serum or supernatant by centrifugation at 10,000 x g for 5 minutes. Serum and/ or supernatant was diluted 1:2 with serum matrix before plating and following the manufacturer’s protocol for Milliplex Human Cytokine/Chemokine MAGNETIC BEAD Premixed 38 Plex Kit (HCYTMAG-60K-PX38, Millipore Sigma, Ontario, Canada). Data were collected using a Luminex (Millipore Sigma, Ontario, Canada) and analyzed with Belysa Immunoassay Curve Fitting Software (Millipore Sigma, Ontario, Canada) and Microsoft Excel (Microsoft, Redmond, WA, USA). Significant findings were determined and reported with Prism Graph Pad (La Jolla, CA, USA). Statistical Analysis and Figures In vitro and in vivo experiments were performed using technical and biological replicates for appropriate statistical analyses.2-way or 1-way ANOVA were used to evaluate the differences between in vitro EcCAR-MSC and UTD-MSC surface marker expression by % expression and T cell suppression capabilities by absolute T cell count evaluations. ANOVA were also used to determine significant differences between in vivo EcCAR-MSC- treated mice and UTD-MSC-treated mice through IVIS imaging of luciferase ⁺ tumors and luciferase ⁺ MSCs, weight comparisons, blood composition by flow, and GVHD clinical score comparisons. Kaplan Meier survival analyses with Cox Regression were used to determine significance of differences and adjust for confounders (e.g., sex) in survival outcomes in tumor and GVHD xenograft models. To make multiple comparisons between each individual group in previously described analyses, Tukey’s multiple comparisons test supplemented ANOVA analyses. For comparison between two groups, a two tailed unpaired Student’s t- test was used in place of ANOVA. RNA-seq data was processed with DeSeq2 program where raw counts were normalized across the samples (geometric mean), and Benjamini-Hochberg procedure was used for multiple hypothesis correction. All relevant statistically significant comparisons were demarked with asterisks corresponding to levels of significance below p?0.05 indicating a 95% confidence interval (where ns=p?0.05, *p?0.05, **p?0.01, ***p?0.001, and ****p?0.0001). End data points without asterisks represent not significant (ns) differences between groups. Relevant data depict the mean of all data points with either standard deviation (SD) or standard error of the mean (SEM) used to determine error bars. Prism Graph Pad (La Jolla, CA, USA) and Microsoft Excel (Microsoft, Redmond, WA, USA) were used to analyze and create the experimental data figures. Finally, canonical pathway enrichments and molecular networks were generated with significant findings (*padj?0.05) reported by Ingenuity Pathway Analysis (QIAGEN, Redwood City, CA, USA). Results MSCs are successfully transduced with stable CAR expression Using lentiviral vectors augmented with polycation enhancer, efficient transduction of CAR onto MSCs was established. The delivery of CAR-loaded lentivirus was first optimized with protamine sulfate yielding ?70% transduction efficiency on healthy donor adipose- derived MSCs (Figure 15A). Following optimization using a standardized CAR vector, alternative CAR constructs were developed for CAR-MSCs immune-mediated disease therapy. The primary CAR-MSC construct was directed to Ecad, a ligand expressed on inflamed intestinal epithelial cells involved in Graph versus Host Disease (GVHD). GVHD results from donor T cells attacking host epithelial tissues in part through the interaction of T cell integrins with E-cadherin (Ecad) expressed on the gastrointestinal tract. To redirect MSCs to Ecad ⁺ tissue susceptible to immune attack, several anti-Ecad scFv clones were generated for CAR incorporation by phage display. An optimized scFv sequence (hmcECAD.6 (SEQ ID NO:90), Figures 23A-23B) was selected with human, mouse (Figures 23C-23D), and canine cross-reactivity to enable preclinical testing in animal models. To determine if the inclusion of CAR signaling domains would enhance MSC immunosuppressive function without risking cytotoxic T cell conversion, CAR constructs containing CD28? signaling domains were tested. hmcECAD.6 was incorporated into a CAR CD28? backbone (Figure 23B) to generate EcCAR-MSCs (Figure 15B). Stable EcCAR expression was maintained through multiple ex vivo passages with ≥90% transduction efficiency across various MSC donors (Figure 15C-15D and Table 5). EcCAR-MSCs retain their stemness To rule out any unwanted differentiation induced by CAR-MSC engineering, EcCAR-MSC stem phenotype, morphology, and gene expression were determined. Based on MSC stem maintenance criteria set by the International Society for Cell & Gene Therapy, EcCAR-MSCs maintained their stem phenotype and morphology, similar to untransduced (UTD)-MSCs (Figure 15E and Figures 24A-24C). Bulk RNA sequencing (RNAseq) between EcCAR-MSCs and UTD-MSCs was also used to identify phenotypic gene set enrichments. Adipose-derived stem cell phenotypes were enriched in upregulated EcCAR-MSC genes, while differentiated cell lineages were enriched in downregulated genes (Figure 15F). These results support maintained stemness following MSC engineering with limited differentiation induced by CAR transduction. EcCAR-MSCs exhibit superior antigen-specific immunosuppression with maintained stemness The ability of CAR-MSCs to suppress T cells was next tested in vitro. Briefly, EcCAR-MSCs or UTD-MSCs (suppressors) were cocultured for 24-hours with activated T cells (effectors), in the presence or absence of Ecad protein as a strategy to stimulate CAR (stimulator). Both soluble Ecad protein and NALM6 cell lines engineered to stably overexpress Ecad (Figure 16A) were used as sources for CAR stimulation. EcCAR-MSC stimulation by soluble Ecad led to a dose-dependent, superior suppression of T cells as compared to UTD-MSC controls (Figure 16B). MSC stem phenotypes were notably maintained following stimulation through soluble Ecad (Figure 16C). Additionally, EcCAR- MSCs stimulated by Ecad ⁺ cell line also displayed antigen-specific immunosuppression. Superior T cell suppression was achieved following cocultures of EcCAR-MSCs with Ecad ⁺ cells, but not Ecad- cells, across multiple MSC donors (Figures 16D-16F). Stimulation by Ecad ⁺ or Ecad- cell lines also did not affect the stemness properties or morphology of EcCAR-MSCs (Figure 16G and Figures 24B-24C). EcCAR-MSCs suppress the antitumor activity of CART19 in tumor xenograft models Based on these findings in vitro, and to determine if CAR-MSCs suppress CART19 and enhance tumor growth in an antigen-specific context, CAR-MSC immunosuppression was evaluated in vivo through tumor and GVHD xenograft models. In tumor models, the ability of MSCs to suppress the potent anti-tumor activities of CD19-targeted T cells (CART19) was measured (Figure 17A). To provide antigen-specific stimulation for EcCAR- MSCs, Ecad ⁺ NALM6 cells and Ecad- NALM6 cells were used as controls (Figure 16A). Tumor models were established by intravenous (i.v.) administration of luciferase ⁺ Ecad ⁺ NALM6 or luciferase ⁺ Ecad- NALM6 tumor cells into immunocompromised NOD-SCID-? ^-/- (NSG) mice (Figure 17A). It was determined that the growth of Ecad ⁺ NALM6 and Ecad- NALM6 in immunocompromised mice without additional treatment was similar (Figure 25A). Following engraftment, mice were randomized based on tumor burden as determined by bioluminescent imaging (BLI) to treatment with CART19 plus UTD-MSCs, or CART19 plus EcCAR-MSCs with tumor burdens assessed through biweekly BLI. Results indicated an Ecad dependent activation of EcCAR-MSCs in vivo. Treatment of Ecad ⁺ NALM6 (Figure 17B), but not Ecad- NALM6 (Figure 17C) xenograft mice with EcCAR-MSCs resulted in dampened antitumor activity, as compared to treatment with UTD-MSCs. EcCAR-MSCs did not directly promote leukemic growth alone in NALM6 cocultures (Figures 25B-25C). It was also found that EcCAR-MSC treatment significantly impairs the antitumor activity and decreases survival in tumor xenograft models when coinjected with irradiated Ecad ⁺ MCF7 as an alternative strategy to stimulate EcCAR-MSCs (Figures 25D-25G). These results highlight the potent immunosuppressive potential of EcCAR-MSCs in the presence of Ecad antigen in vivo. EcCAR-MSCs improve therapeutic outcomes and display antigen-specific trafficking to Ecad ⁺ target sites in GVHD xenograft models The therapeutic efficacy of EcCAR-MSCs was tested in GVHD xenograft models. GVHD xenograft models were generated through the i.v. administration of human peripheral blood mononuclear cells (PBMCs) into NSG mice. See, for example, Ehx et al. Front Immunol 9, 1943 (2018). Mice received intraperitoneal (i.p.) doses of PBS control, UTD- MSCs, or EcCAR-MSCs as a form of GVHD treatment (Figure 17D). GVHD progression was recorded through bodyweight measurements, clinical GVHD symptom scoring (Table 4), and survival outcomes. EcCAR-MSC treatment prevented bodyweight loss (Figure 17E), ameliorated clinical GVHD symptoms (including fur, skin integrity, posture, and activity) (Figure 17F), and improved the overall survival (Figure 17G) as compared to mice receiving UTD-MSCs or no MSC treatment. To evaluate the impact of the anti-Ecad scFv contained within EcCAR-MSCs, the efficacy of EcCAR-MSCs was compared to CAR-MSCs containing an scFv of irrelevant specificity to mouse tissue (anti-CD19 CAR-MSC). Specifically, antigen-specific stimulation and trafficking of EcCAR-MSCs to Ecad ⁺ epithelia within the colon of GVHD xenograft mice was assessed. GFP ⁺ luciferase ⁺ EcCAR-MSCs and GFP ⁺ luciferase ⁺ control anti-CD19 CAR-MSCs were generated (Figures 26A-26B). Trafficking and efficacy of the GFP ⁺ luciferase ⁺ EcCAR-MSCs and GFP ⁺ luciferase ⁺ control anti-CD19 CAR-MSCs in a GVHD xenograft model (Figure 18A). In this model, mice were irradiated prior to PBMC and MSC injection to induce a more severe GVHD phenotype (which will be referred to as ‘acute GVHD model’) in which mice develop acute GVHD within one week of PBMC injection. See, for example, Schroeder and DiPersio. Dis. Model Mech.4, 318-333 (2011). In this acute GVHD model, EcCAR-MSC treatment again led to a significant reduction in weight loss (Figure 18B) and prolonged survival (Figure 18C) of mice as compared to control CD19- CAR-MSCs or no MSCs. To elucidate the mechanism underlying increased EcCAR-MSC efficacy in this model, mouse peripheral blood was also collected two weeks following MSC injections and analyzed for human T cells. The administration of EcCAR-MSCs led to an increased suppression of human T cells in the peripheral blood as compared to CD19 CAR MSC and no MSC treated control mice (Figure 18D). One week following CAR-MSC injection, satellite mice from these experiments were euthanized, and organs were harvested and analyzed for the presence of CAR-MSCs both by BLI and immunofluorescence. Both BLI and immunofluorescent assessment of mouse colonic tissues following MSC treatment demonstrated superior infiltration of EcCAR-MSCs within Ecad ⁺ colon tissues as compared to CD19-CAR-MSCs (Figures 18E-18G). Collectively, these results indicate enhanced immunosuppressive efficacy and target tissue trafficking by EcCAR-MSCs in the GVHD models. EcCAR-MSC stimulation induces an immunosuppressive phenotype through the activation of signaling pathways, suppressive cytokines, and surface receptors To evaluate the mechanisms of immunosuppressive enhancement in EcCAR-MSCs, gene expression, cytokine secretion, and surface marker profiles of stimulated EcCAR-MSCs were surveyed. Gene expression profiles were first analyzed through bulk RNAseq across the following conditions: UTD-MSCs (nonstimulated), UTD-MSCs (stimulated with soluble Ecad as a control), EcCAR-MSCs (nonstimulated), and EcCAR-MSCs (stimulated with soluble Ecad to test antigen-specific CAR stimulation). Pathway enrichments were identified between conditions through predictive networks generated in Ingenuity Pathway Analysis (IPA) machine learning software. To characterize the impact of CAR transduction on MSCs, nonstimulated EcCAR- MSC vs. UTD-MSC samples were compared. While 331 genes were significantly upregulated between groups, gene enrichments were mostly attributed to cellular stress response pathways that are commonly induced by lentiviral transduction (Figures 27A-27C). Notably, these enrichments become insignificant between stimulated EcCAR-MSCs vs. UTD-MSCs, instead revealing predominant homeostatic pathway enrichments (Figure 27D). Unbiased hierarchical gene clustering across all conditions indicated that the most evident changes to gene expression were driven by antigen-specific stimulation of EcCAR- MSCs(+Ecad) creating a cluster distinguished from all other conditions (Figure 19A). To characterize the impact of CAR antigen-specific CD28? stimulation, Ecad- stimulated EcCAR-MSC samples were compared to nonstimulated EcCAR-MSC samples. Activation of 1662 upregulated genes was identified (Figure 27A), supporting that while CAR transduction modifies MSC gene expression, CAR stimulation results in more striking changes to gene activation (Figure 19A). Principal component analyses of gene expression across Ecad-stimulated and nonstimulated conditions revealed a propensity for UTD-MSC samples to cluster by their derived MSC biological donor (Figure 19B), while EcCAR-MSC samples instead clustered by Ecad stimulation status (Figure 19C). Canonical pathways significantly upregulated by CAR stimulation were robustly linked to MSC anti- inflammatory interleukins (IL-6 and IL-10), NFkB, tumor necrosis factor receptor 2(TNFR2), and toll-like-receptor (TLR) signaling pathways (Figures 19D-19E). These pathways each contribute to MSC immunosuppressive function through either cytokine- mediated T cell suppression, the induction of Tregs, or direct receptor interactions. Gene counts of transcription factors (NFkB1, JUN, RELB, IRF1) and concomitant regulatory factors (TRAF1, TLR3, and FYN) were robustly elevated in Ecad-stimulated EcCAR-MSC samples (Figure 19F). Altogether, these transcription factors, among others identified following CAR stimulation, were also identified as direct downstream targets of CD28 stimulatory molecule (Figure 19D), and as regulators of MSC immunosuppressive function. Apoptosis of leukocytes was identified as a significant functional enrichment between all signaling molecules contained in the predictive network for EcCAR-MSC stimulation (Figure 19D). To understand how gene activation in EcCAR-MSCs may translate to functional immunosuppression, the expression of inhibitory receptors and human cytokine production following antigen specific stimulation of EcCAR-MSCs were measured. Antigen-specific stimulation of EcCAR-MSCs (with Ecad ⁺ cell lines) resulted in increased secretion of suppressive cytokines in vitro, such as interleukin 10 (IL-10), interleukin 4 (IL-4), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor (VEGF) (Figure 20A), as compared to co-culture of EcCAR-MSC with activated T cells in the presence of Ecad- cell lines. Additionally, there was an antigen-dependent increase in critical inhibitory surface markers galectin-9 (Gal-9) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in stimulated EcCAR-MSCs (Figure 20B). Human cytokine production was measured in the serum of mice 2 weeks after EcCAR MSC or UTD MSC treatment in the tumor model (Figure 17A). Elevation of IL-10, G-CSF, and eotaxin, among other cytokines in EcCAR-MSC-treated mice were found (Figure 20C and Figure 27E). The peripheral blood was also assessed for human CD3 ⁺ T cell subtypes in GVHD xenograft mice treated with EcCAR-MSCs compared to UTD-MSCs. In correlation with a significant prevention of weight loss (Figures 20D-20H), mice treated with EcCAR-MSCs demonstrated a significantly suppressed absolute numbers of human CD3 ⁺ T cells circulating in the peripheral blood (Figure 20E). Although both human CD4 ⁺ and CD8 ⁺ T cells were suppressed in EcCAR-MSC-treated mice (Figure 20F), an increase in the proportion of human CD4 ⁺ T cells was identified 2 weeks post-treatment in EcCAR-MSC-treated mice (Figure 20G). Analysis of peripheral blood 4 weeks post-treatment also indicated an enrichment of Tregs (human CD4 ⁺ , CD25 ⁺ , CD127-) in EcCAR-MSC-treated mice compared to UTD-MSC-treated mice (Figure 20H). Altogether, these findings indicated enhanced T cell suppression after antigen specific stimulation of EcCAR-MSCs, and demonstrated an association with activation of immunosuppressive pathways, increased production of inhibitory cytokines and upregulation of inhibitory receptors, as compared to unstimulated EcCAR-MSCs. Incorporation of CD28? signaling domain in CAR-MSCs is required for enhanced immunosuppressive activity To determine which components of the CD28ζ signaling domains are required to drive EcCAR-MSC-mediated enhanced immunosuppression following their antigen specific stimulation, CD28-stimulated EcCAR-MSCs (CD28 EcCAR-MSC), CD3 ζ-stimulated EcCAR-MSCs (CD3 ζ EcCAR-MSC), and EcCAR-MSCs lacking intracellular domains (Null EcCAR-MSC) were generated and compared to CD28-CD3 ζ-stimulated EcCAR-MSCs (CD28ζ EcCAR-MSC) (Figure 21A-21B). CD28ζ EcCAR-MSCs and CD28 EcCAR-MSCs showed antigen-specific suppression of activated T cells, while CD3 ζ EcCAR-MSCs, Null EcCAR-MSCs, and UTD-MSCs did not (Figure 21C), indicating a role for CD28 signaling in CAR-MSC immunosuppressive properties. The impact of CAR signaling domain incorporation was also tested in the acute GVHD xenograft model (Figure 21D). In this model, treatment with CD28ζ EcCAR-MSCs resulted in the prevention of weight loss (Figure 21E), the lowest clinical GVHD symptom severity score (Figure 17F), and the longest overall survival (Figure 17G) when compared to mice treated with CD28, CD3 ζ, or null signaling domain EcCAR-MSCs. CD28 EcCAR-MSCs treatment also resulted in ameliorated weight loss and overall survival that was numerically, but not statistically, inferior to CD28ζ EcCAR-MSC. These data suggest that while CD28 alone confers immunosuppressive capabilities in EcCAR-MSCs, CD28ζ incorporated in EcCAR-MSCs results in enhanced immunosuppressive treatment outcomes. EcCAR-MSCs are safe in animal models Following functional interrogation, studies were performed to ensure allogeneic EcCAR-MSC safety. First, EcCAR-MSC expansion and clearance was defined in NSG mice, using luciferase ⁺ EcCAR-MSCs and UTD-MSCs (Figure 22A and Figure 26A). MSC persistence was monitored in mice with or without irradiated human Ecad ⁺ MCF7 cells to understand the impact of antigen-specific stimulation on MSC clearance. Mice were treated with 1) luciferase ⁺ UTD-MSCs alone, 2) luciferase ⁺ UTD-MSCs plus human Ecad ⁺ cells, 3) luciferase ⁺ EcCAR-MSCs alone, or 4) luciferase ⁺ EcCAR-MSCs plus human Ecad ⁺ cells (Figure 22A). Serial BLIs were performed every 2-3 days for MSC quantification. These studies revealed no significant difference between the clearance time (~30 days) of UTD- MSCs and EcCAR-MSCs with or without additional target antigen stimulation, further supporting the safety profile of EcCAR-MSCs (Figures 22B-22C). Then, the toxicity of EcCAR-MSCs on normal epithelial tissues expressing Ecad was determined. First, the effect of EcCAR-MSCs on Ecad ⁺ keratinocytes derived from healthy donors was determined. Co-cultures of EcCAR-MSCs with keratinocytes resulted in no significant differences in survival of keratinocytes as compared to co-cultures with UTD- MSCs (Figure 22D). These cocultures also did not appear to significantly impact expression of Ecad on keratinocyte target cells (Figure 22E). Evaluation of coculture supernatants indicate antigen specific stimulation of EcCAR-MSC as evident by upregulation in cytokines including IL-10, IL-4, and eotaxin (Figure 22F). Second, the toxicity of EcCAR-MSCs on Ecad ⁺ bronchial cells was determined. Cocultures of Ecad ⁺ bronchial cells with EcCAR-MSCs had no apparent impact on bronchial cell survival as compared to cocultures with UTD-MSCs (Figure 22G). Additionally, no trafficking of EcCAR-MSCs to the lungs was observed as determined by immunofluorescence assessment of lungs harvested 1 week following EcCAR-MSC treatment in the GVHD xenograft model (Figures 22H-22I). Canine models were used to assess if any toxicities were associated with administration of human EcCAR-MSCs containing canine cross-reactive scFv (Figure 23A). Healthy canines received EcCAR-MSCs by i.p. injection and were monitored for safety outcomes and tissue integrity for 28 days. (Figure 28A). Toxicity was assessed by serial measurements of complete blood counts, liver, and kidney functions. EcCAR-MSCs were not associated with hematopoietic toxicity (Figure 28B), organ toxicity (Figure 28C), weight loss (Figure 28D), or tissue damage (Figure 28E), indicating a strong safety profile and lack of toxicity induced by EcCAR-MSC administration. Together, these results demonstrate that CAR-MSC generation provides antigen- specific immunosuppressive activation designed to augment MSC therapy safely. Example 5: Treating GVHD Ecad-CAR-MSCs engineered to express one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides are administered to a human identified as having or as being at risk of developing GVHD. The CAR-MSCs engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides are administered using intravenous injection. After the administration of the one or more CAR- MSCs engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides, the number of activated T cells within the human is reduced. After the administration of the one or more CAR-MSCs engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides, one or more symptoms of GVHD within the human are reduced. Example 6: Treating GVHD MSCs engineered to express a CAR targeting an epithelial specific antigen and engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides are administered to a human identified as having or as being at risk of developing GVHD. The MSC engineered to express a CAR targeting an epithelial specific antigen and engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides are administered using intravenous injection. After the administration of the one or more MSC engineered to express a CAR targeting an epithelial specific antigen and engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides, the number of activated T cells within the human is reduced. After the administration of the one or more MSC engineered to express a CAR targeting an epithelial specific antigen and engineered to express an elevated level of one or more polypeptides selected from NFkB1 polypeptides, JUN polypeptides, RELB polypeptides, IRF1 polypeptides, TNFα polypeptides, IL-10 polypeptides, FGF-2 polypeptides, PD-1, polypeptides, G-CSF polypeptides, GM-CSF polypeptides, eotaxin polypeptides, Gal-9 polypeptides, PD-1 polypeptides, TIM-3 polypeptides, CXCR3 polypeptides, and CXCR4 polypeptides, one or more symptoms of GVHD within the human are reduced. OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.