# Engineered Regulatory T cells with Enhanced Stability and Suppression for Autoimmunity

> **NIH NIH F31** · STANFORD UNIVERSITY · 2021 · $38,849

## Abstract

PROJECT SUMMARY
Autoimmune diseases are characterized by the immune system attacking the body, adversely affecting over 23
million Americans a year. Current standards of care often only alleviate symptoms, leave patients dependent on
therapies, and increase their susceptibility to infection, necessitating new treatment paradigms. The recent
development of engineered cell-based therapies has allowed us to harness a suppressive T cell phenotype
known as regulatory T cells (Tregs) and design them to target sites of autoimmunity. However, instability of the
Treg phenotype and inability to drive immunosuppressive functions have hindered their therapeutic potential and
widespread adoption in the clinic. We seek to harness novel technologies from genome and receptor engineering
to build a platform for engineering of highly stable and suppressive Tregs that become the basis for future cell-
based therapies against autoimmunity. This platform is enabled by two novel cell engineering techniques that I
recently developed, including a highly efficient and specific knock-in strategy that stabilizes transgene expression
and a receptor platform that activates customized cytokine pathways. Specifically, we aim to 1) generate a highly
stable Treg phenotype by leveraging the knock-in strategy to express the Treg driving transcription factor, FOXP3,
in CD4+ T cells, 2) identify and characterize suppression enhancement pathways by high-throughput cell-based
screens utilizing my receptor platform, and 3) assess the therapeutic benefit of these novel engineered Tregs in a
mouse model of Graft-vs-Host Disease. This work results in a novel discovery and engineering platform that
creates Tregs that can be adapted for targeted cell-based therapies against a plethora of autoimmune diseases.
The completion of the proposed work creates new data, new pathways, and new technologies to improve the
survival and the function of Treg therapies, improving their translation potential and bringing them closer to helping
the people who need it most.

## Key facts

- **NIH application ID:** 10314662
- **Project number:** 1F31AI164936-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** MICHAEL GREGORY CHAVEZ
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,849
- **Award type:** 1
- **Project period:** 2022-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314662

## Citation

> US National Institutes of Health, RePORTER application 10314662, Engineered Regulatory T cells with Enhanced Stability and Suppression for Autoimmunity (1F31AI164936-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10314662. Licensed CC0.

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