[Pubmed] Engineered Bi-Specific AChR CAAR T Cells for Selective Elimination of Myasthenia Gravis B Cells
Posté : 27 mars 2026 11:00
Res Sq [Preprint]. 2026 Mar 20:rs.3.rs-9094407. doi: 10.21203/rs.3.rs-9094407/v1.
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.
PMID:41890833 | PMC:PMC13015596 | DOI:10.21203/rs.3.rs-9094407/v1
Source: https://pubmed.ncbi.nlm.nih.gov/4189083 ... t6+133c1fe