# iSTAR Tregs

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $968,858

## Abstract

ABSTRACT
Regulatory T cells (Tregs) are a small subset of T cells that are vital to immune self-tolerance. They
function by dominantly controlling the activities of other immune cells. In mouse models of type 1 diabetes
(T1D), a single infusion of islet-specific Tregs prevents and stably reverses autoimmune diabetes. In these
mouse models, infused Tregs accumulate in pancreatic islets and arrest autoimmune aggression against
islet beta cells by expressing immune suppressive functions locally.
Early-phase clinical trials of Treg cell therapy in patients with T1D have shown that it is feasible to produce
billions of patients’ own Tregs for infusion and the therapy is well tolerated and safe. These pioneering
efforts have paved the way for the development of next-generation Treg therapy aiming at establishing
efficacy. The research program described in this proposal focuses on a critical need for a strategy to
increase effectiveness by targeting human Tregs to the pancreatic islets and to monitor the targeting
efficacy in patients.
The proposed strategy is guided by the overarching hypothesis that shared, dominant immunopeptides
on the surface of beta cells are highly specific anchors for islet targeting. Tregs can be engineered to
target these anchors to deliver their immune regulatory function locally in the islets. Moreover, successful
engagement of Tregs with beta cells can be monitored using an engineered biomarker released into the
peripheral blood.
Aim 1 will define the immunopeptidome of pancreatic beta cells. Aim 2 will develop a cellular engineering
strategy to target Tregs efficiently and safely to pancreatic islets. Aim 3 will develop a barcode biomarker
that is released by activated Tregs into the peripheral blood. These projects together aim to develop islet-
specific TCR activation relay (iSTAR) Tregs. We have built a team of three investigators with
complementary expertise in immunology, beta cell biology, and technology development. The proposed
program synergizes our expertise to tackle the challenges in precision targeting of pancreatic islets for
the preservation of beta cell mass in T1D.

## Key facts

- **NIH application ID:** 10871893
- **Project number:** 5U01DK137140-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MICHAEL T MCMANUS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $968,858
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871893

## Citation

> US National Institutes of Health, RePORTER application 10871893, iSTAR Tregs (5U01DK137140-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871893. Licensed CC0.

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