# Engineering CAR Tregs for type 1 diabetes

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2022 · $231,545

## Abstract

Summary
Type 1 diabetes (T1D) results from a breakdown in immunological tolerance and the resulting T cell-
mediated destruction of insulin producing beta cells in the pancreas. This is caused by defective
“regulatory” T cells (or Tregs), which normally suppress harmful immune responses. In T1D, Tregs stop
protecting beta cells. Work from T1D animal models has shown that therapeutic restoration of Tregs can
prevent disease progression, and clinical studies have shown the safety of this approach in humans.
Despite this initial success, there are significant hurdles for long term and global Treg therapy in T1D.
Current methods infuse large numbers of polyclonal Tregs that have not been selected for antigen
specificity, so they carry the risk of non-specific immunosuppression. Furthermore, it is difficult to expand
enough of these polyclonal Tregs required for therapy, and even then, only a small fraction of the cells
actually suppress autoimmunity. These challenges can be solved by creating “designer” Tregs that are
engineered for specificity and have the best chance of resetting immune tolerance. If successful, this
technology would lead to a more personalized and effective T1D immunotherapy. We recently developed
an approach to engineer antigen-specific Tregs by re-directing their specificity using chimeric antigen
receptors, or CARs. In this application, we will test if peptide specific MHC-CAR-Tregs prevent and/or
reverse T1D in NOD mice. We hypothesize that mouse Tregs expressing a hybrid insulin peptide-MHCII-
specific CAR will prevent T1D by restoring immune tolerance and suppressing autoreactive effector CD4+
and CD8+ T cell function to limit their accumulation in the pancreas.

## Key facts

- **NIH application ID:** 10495238
- **Project number:** 5R21AI166475-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Brian T Fife
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $231,545
- **Award type:** 5
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495238

## Citation

> US National Institutes of Health, RePORTER application 10495238, Engineering CAR Tregs for type 1 diabetes (5R21AI166475-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10495238. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*