{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:40:08Z","timestamp":1791859208614,"version":"4.3.4"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"9","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:p>In acetylcholine receptor (AChR)\u2013seropositive 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\u2013amino acid extracellular domain of the AChR \u03b1 subunit (A210) linked to CD137-CD3\u03b6 cytoplasmic domains to direct T cell cytotoxicity against anti-AChR\u03b1 B cells. A210-CAART incorporating a CD8\u03b1 transmembrane domain (TMD8\u03b1) 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.TMD8\u03b1-CAART demonstrated early control of anti-AChR B cell outgrowth but subsequent rebound and loss of surface CAAR expression, whereas A210.TMD28-CAART induced sustained surface CAAR expression and target cell elimination. This study demonstrates the importance of the CD28 TMD for CAAR stability and in vivo function, laying the groundwork for future development of precision cellular immunotherapy for AChR-MG.<\/jats:p>","DOI":"10.1126\/sciadv.adt0795","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T13:58:57Z","timestamp":1740751137000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0092-9031","authenticated-orcid":true,"given":"Sangwook","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania, Philadelphia, PA, 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