Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis.

ABSTRACT: In acetylcholine receptor (AChR)-seropositive myasthenia gravis (MG), anti-AChR autoantibodies impair neuromuscular transmission and cause severe muscle weakness. MG therapies broadly suppress immune function, risking infections. We designed a chimeric autoantibody receptor (CAAR) expressing the 210-amino acid extracellular domain of the AChR α subunit (A210) linked to CD137-CD3ζ cytoplasmic domains to direct T cell cytotoxicity against anti-AChRα B cells. A210-CAART incorporating a CD8α transmembrane domain (TMD8α) showed functional but unstable surface expression, partially restored by inhibiting lysosomal degradation. A210-CAART with a CD28 TMD showed sustained surface expression, independent of TMD dimerization motifs. In a mouse xenograft model, A210.TMD8α-CAART demonstrated early con

SUBMITTER: Oh S 

PROVIDER: S-EPMC11870065 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature