Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models
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.
Authors
- Sonja Blumenau (ORCID: https://orcid.org/0000-0002-6606-3800)
- Stephanie Wernick
- Gregorio Spagni (ORCID: https://orcid.org/0000-0003-0656-9671)
- Kevin C. O’Connor (ORCID: https://orcid.org/0000-0002-7056-419X)
- Maria Stecklum (ORCID: https://orcid.org/0009-0001-7951-5730)
- Andreas Pelz (ORCID: https://orcid.org/0000-0002-7111-6970)
- Lucie Y. Li (ORCID: https://orcid.org/0000-0001-8098-1977)
- Harald Prüß (ORCID: https://orcid.org/0000-0002-8283-7976)
- S. Momsen Reincke (ORCID: https://orcid.org/0000-0002-8132-3527)
- Niels von Wardenburg (ORCID: https://orcid.org/0000-0003-0476-9813)
- Hans‐Christian Kornau (ORCID: https://orcid.org/0000-0003-4187-7549)
- Viktoria Zinnow
- Andreas Meisel (ORCID: https://orcid.org/0000-0001-7233-5342)
- Nicholas Sanderson (ORCID: https://orcid.org/0000-0003-1711-7275)
- Minh Pham (ORCID: https://orcid.org/0000-0003-0234-4790)
- Dietmar Schmitz (ORCID: https://orcid.org/0000-0003-2741-5241)
- Tobias Derfuss (ORCID: https://orcid.org/0000-0001-8431-8769)
- Amelya Keles (ORCID: https://orcid.org/0000-0001-5328-2740)
- Marie A. Homeyer
- Valentina Damato
Institutions
- University of Basel (CH)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital of Basel (CH)
- Yale University (US)
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Bernstein Center for Computational Neuroscience Berlin (DE)
- Einstein Center for Neurosciences Berlin (DE)
- University of Florence (IT)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-08-20
- DOI
- https://doi.org/10.1038/s41467-026-76750-7
- Primary Topic
- Myasthenia Gravis and Thymoma
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Rare Diseases Clinical Research Network
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Ministero della Salute
- European Academy of Neurology
- Berlin Institute of Health
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases