# Engineered Mesenchymal Stromal Cells for Enhanced Immunosuppression

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $777,522

## Abstract

PROJECT SUMMARY
Mesenchymal stromal cells (MSCs) have regenerative, immunosuppressive properties, but using MSCs to treat
autoimmunity has resulted in mixed clinical results at best. Lackluster therapeutic efficacy has been attributed to
insufficient trafficking to the tissue of interest and suboptimal immunosuppression. Our preliminary data indicate
that using lentiviruses with specific enhancers, we can successfully engineer MSCs to express chimeric antigen
receptors (CARs) and become CAR-MSC. We also have demonstrated that incorporating specifically designed
CARs targeting gut integrins into MSCs results in their enhanced immunosuppression and trafficking to the colon
in preclinical models. Engineering MSCs maintain their stemness and CAR-MSCs are safe in canine models.
This led to our central hypothesis that engineering MSCs with a CAR enhances their efficacy in graft versus host
disease (GVHD) and autoimmune inflammatory bowel disease (IBD) and colitis. In this project, we will leverage
our available tools of viral vectors, CRISPR constructs, mouse models, and established biobanks to develop
CAR-MSCs that demonstrate enhanced therapeutic efficacy over unmodified MSCs in the treatment of GVHD.
In Aim 1 of this proposal, we will determine the mechanisms by which CAR-MSCs exert their enhanced
immunosuppression. In Aim 2 of this proposal, we will study cellular trafficking in preclinical models. In Aim 3 of
this proposal, we will optimize signaling of CAR-MSCs. At the conclusion of this project, we will have developed
a new, translatable cellular therapeutic strategy to treat GVHD and IBD by engineering CAR-MSCs to have
improved targeting and immunosuppression over unmodified MSCs. This platform can be applicable in different
autoimmune diseases.

## Key facts

- **NIH application ID:** 10981063
- **Project number:** 1R01AI179974-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Saad J. Kenderian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $777,522
- **Award type:** 1
- **Project period:** 2024-07-11 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981063

## Citation

> US National Institutes of Health, RePORTER application 10981063, Engineered Mesenchymal Stromal Cells for Enhanced Immunosuppression (1R01AI179974-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10981063. Licensed CC0.

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