Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models
- Niels von Wardenburg
- Gregorio Spagni
- S. Momsen Reincke
- Stephanie Wernick
- Hans-Christian Kornau
- Viktoria Zinnow
- Amelya Keles Slevogt
- Lucie Y. Li
- Marie A. Homeyer
- Sonja Blumenau
- Maria Stecklum
- Dietmar Schmitz
- Andreas Pelz
- Valentina Damato
- Nicholas Sanderson
- Tobias Derfuss
- Minh C. Pham
- Kevin C. O’Connor
- Andreas Meisel
- Harald Prüss
2026-08-20
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder mediated 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 AChRα1 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 a xenograft mouse model, 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.