# Precise targeting of T1D specific T cells using CAR and peptide-MHC chimeric antigen ligands

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $769,703

## Abstract

Project Summary
Type 1 diabetes (T1D) is an incurable autoimmune disease manifested through the immune destruction of islet
beta cells. This proposal describes a unique CAR T cell approach to eliminate islet-autoreactive T cells, thus
eliminating the source of the autoimmunity and providing a highly specific treatment for T1D. We will leverage
our recently developed split CAR system with a chimeric antigen ligand (CAL) adaptor consisting of a pMHC
multimer fused to a recruitment molecule. The addition of CAL will bind to the autoreactive TCR and recruit the
universal CAR T cells to kill autoreactive T1D specific T cells. The proposed experiments will test the hypoth-
eses that (1) our modular CAR/CAL systems are uniquely suited for specifically targeting multiple auto-
reactive TCRs, and (2) that we can identify novel epitopes against T1D specific TCRs to be paired with
the CAR/CAL system. Importantly, preliminary data support these hypotheses, and well-characterized clinical
specimens from T1D patients and rigorous experimental designs are established in this proposal with essential
cross-disciplinary collaborations and expertise that encompass synthetic biology, large-scale epitope discovery,
T1D immunology, and humanized T1D animal modeling. The specific aims of this five-year proposal are as
follows: Aim 1 establish and optimize the CAL system against antigen-specific human TCRs, Aim 2 characterize
the autoreactivity of TCRs from T1D patients/donors and identify peptide-MHC against these TCRs, and Aim 3
evaluate the performance of the CAL system in humanized T1D animal models. Outcomes from this work will
establish the clinical potential of the CAR/CAL system as a safe, effective, and potentially curative T1D treatment.

## Key facts

- **NIH application ID:** 10906648
- **Project number:** 5R01DK132576-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Michael Birnbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $769,703
- **Award type:** 5
- **Project period:** 2022-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906648

## Citation

> US National Institutes of Health, RePORTER application 10906648, Precise targeting of T1D specific T cells using CAR and peptide-MHC chimeric antigen ligands (5R01DK132576-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10906648. Licensed CC0.

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