[Pubmed] Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthen

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Nat Commun. 2026 Aug 20;17(1):8730. doi: 10.1038/s41467-026-76750-7.

ABSTRACT

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.

PMID:42624846 | DOI:10.1038/s41467-026-76750-7


Source: https://pubmed.ncbi.nlm.nih.gov/4262484 ... 5&v=2.20.1