# Engineered Bi-Specific AChR CAAR T Cells for Selective Elimination of Myasthenia Gravis B Cells

## TL;DR

Researchers developed a new type of T cell therapy that specifically targets and eliminates harmful B cells in myasthenia gravis, a neuromuscular autoimmune disease.

## Contribution

The novelty lies in engineering bi-specific AChR CAAR T cells that selectively target B cells producing anti-AChR autoantibodies.

## Key findings

- AChR CAAR T cells efficiently secreted cytokines and lysed target cells upon activation.
- In vivo, the therapy reduced pathogenic B cells and autoantibody levels at the neuromuscular junction.
- The approach shows potential for durable remission in refractory myasthenia gravis patients.

## Abstract

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by autoantibodies targeting the nicotinic acetylcholine receptor (nAChR), which can lead to severe disability and life-threatening crises. Current therapies rely on broad immunosuppression and fail to achieve sustained remission in the majority of patients. Here, we report the development of AChR chimeric autoantibody receptor (CAAR) T cells engineered to selectively eliminate autoreactive B cells producing anti-AChR autoantibodies. T cells were co-transduced with CAARs expressing extracellular domains of the AChR α1 or β1 subunits, enabling recognition of a broad range of pathogenic antibodies. AChR CAAR T cells selectively secreted effector cytokines upon activation, and efficiently lysed target cells. In vivo, they depleted pathogenic B cell lines and reduced autoantibody levels in the circulation and at the neuromuscular junction. These findings establish AChR CAAR T cells as a precision immunotherapy with the potential to achieve durable remission in refractory MG.