# Engineering CAR T Cells to Establish Stable Mixed Chimerism in Allogeneic Transplantation

> **NIH NIH F31** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $28,019

## Abstract

Project Summary/Abstract
Hematopoietic stem cell transplantation (HSCT) has become a powerful treatment for a myriad of disorders.
Patients diagnosed with blood disorders such as leukemia or aplastic anemia that are treated with HSCT have
seen highly improved outcomes, and in some of these cases HSCT is the only curative option. However, donors
and recipients of these transplants are commonly not HLA identical, resulting in an immune response due to
interactions between the recipient’s alloreactive memory T cells that recognize “non-self” antigens on the donor
cells. The most common method of inducing tolerance to the donor cells and tissue is by lifelong administration
of immunosuppressive drugs that come with the risk of opportunistic infections and toxicities. The overarching
goal of this project is to develop the necessary genetic tools to restore immune tolerance without the need for
life-long immunosuppression. Our approach to achieving this is to propose a split CAR T cell system that uses
off-the-shelf antibody adapter molecules to specifically deplete the recipient’s memory T cells that are reactive
against the donor, while preserving other T cell subsets to maintain a robust immune system. This system has
the ability to switch targets without reengineering the T cells and respond to multiple antigens to target only
alloreactive T-cells and enhance the establishment of mixed chimerism and transplantation tolerance. If
successful, the findings of this research project will demonstrate the feasibility of using CAR T cell therapy for
the induction of immune tolerance that can be applied beyond HSCT to the treatment of many autoimmune
conditions including type 1 diabetes, rheumatoid arthritis, vitiligo and a myriad of disorders that originate from
autoreactive T cell dysfunction.

## Key facts

- **NIH application ID:** 10537182
- **Project number:** 1F31HL162477-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Menna Yamany Siddiqui
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,019
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537182

## Citation

> US National Institutes of Health, RePORTER application 10537182, Engineering CAR T Cells to Establish Stable Mixed Chimerism in Allogeneic Transplantation (1F31HL162477-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10537182. Licensed CC0.

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