Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models
Year: 2026
Type: article
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.
Source: Nature Communications
Authors: 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
Institutions: German Center for Neurodegenerative Diseases, Humboldt-Universität zu Berlin, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, University of Florence, University of Basel, University Hospital of Basel, Yale University, Center for Stroke Research Berlin
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Amgen, Alexion Pharmaceuticals, Neurocrine Biosciences, Rare Diseases Clinical Research Network, Argenx, Horizon Therapeutics, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Ministero della Salute, European Academy of Neurology, Grifols, Berlin Institute of Health, National Institutes of Health, EMD Serono, National Institute of Allergy and Infectious Diseases
Awards: G1275810520, G161547206, G1998863278, G2044136217, KFO 5023: BECAUSEY Berliner Zentrum für Diagnose, Verständnis und Behandlung von Antikörper(Y)vermittelten neurologischen Erkrankungen, FOR 3004: Pathophysiologie autoimmuner Enzephalitiden – SYNABS, G33247875, G3426671974, G4279768677, G464521655, G5863455821, G751078230, G8142160590, Data Management and Coordinating Center: Rare Diseases Clinical Research Network
OpenAlex ID: W7203827425