# B cell-targeted CAR-T treatment of CNS Autoimmunity

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $236,250

## Abstract

PROJECT SUMMARY
An immense need for selective and antigen-specific immunotherapy without global immunosuppression exists
for autoimmune diseases such as multiple sclerosis (MS). This has prompted exploration of chimeric antigen
receptor (CAR) T cell utilization to specifically eliminate autoreactive cells. The contribution of B cells to MS
and related diseases is recognized in part by the success of B cell depletion therapies. However, depletion of B
cells for neuroimmunologic diseases are not selective enough to avoid safety concerns related to non-specific
B cell depletion, including immunosuppression and infection. Hence, we seek to develop CAR T cells to target
antigen-specific, autoreactive B cells using a B cell-dependent version of experimental autoimmune
encephalomyelitis (EAE), an animal model with relevance to inflammatory demyelinating diseases of the
central nervous system (CNS) such as MS. In preliminary studies, we have created a unique version of CAR T
cells in which peptide MHCII (pMHCII) is fused with signaling domains in order to recognize specific T cell
receptors (TCRs). We demonstrate that these pMHCII-CAR T cells specifically recognize a cognate TCR in
vitro and in vivo and are capable of limiting EAE severity. We now seek to develop antigen-specific B cell
depletion for the treatment of B cell-dependent EAE in two aims. In Aim 1, we will optimize survival of, and
killing by, myelin oligodendrocyte glycoprotein (MOG)-expressing CAR T cells targeting MOG-specific B cells
in both prevention and treatment of EAE. In Aim 2, we will utilize pMHCII-CAR T cells targeting MOG-specific
TCRs in combination with MOG-CAR T cells targeting auto-reactive B cells in EAE. In sum, our proposed
studies will explore the potential of a CAR T cell approach for the treatment of CNS autoimmunity by
addressing how to optimally eliminate TCR and BCR specificities without leading to blanketed
immunosuppression.

## Key facts

- **NIH application ID:** 10514950
- **Project number:** 1R21AI171994-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CHYI S HSIEH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2022-08-05 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514950

## Citation

> US National Institutes of Health, RePORTER application 10514950, B cell-targeted CAR-T treatment of CNS Autoimmunity (1R21AI171994-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10514950. Licensed CC0.

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