Journal Article

DZNE-2026-00908

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Bispecific chimeric autoantibody receptor T cells eliminate acetylcholine receptor-specific B cells in myasthenia gravis models.

von-Wardenburg, N.-O. (First author)DZNE* ; Spagni, G. (First author)DZNE* ; Reincke, S. M. (First author)DZNE* ; Wernick, S.DZNE* ; Kornau, H.-C.DZNE* ; Zinnow, V.DZNE* ; Keles Slevogt, A.DZNE* ; Li, L.Extern* ; Homeyer, M. A.DZNE* ; Blumenau, S.DZNE* ; Stecklum, M. ; Schmitz, D.DZNE* ; Pelz, A. ; Damato, V. ; Sanderson, N. ; Derfuss, T. ; Pham, M. H. ; O'Connor, K. C. ; Meisel, A. ; Prüss, H. (Last author)DZNE*

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-026-76750-7

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.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; B-Lymphocytes: immunology (MeSH) ; Autoantibodies: immunology (MeSH) ; Mice (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; Female (MeSH) ; Receptors, Cholinergic: immunology (MeSH) ; Receptors, Nicotinic: immunology (MeSH) ; Receptors, Nicotinic: genetics (MeSH) ; Myasthenia Gravis: immunology (MeSH) ; Myasthenia Gravis: therapy (MeSH) ; Disease Models, Animal (MeSH) ; Myasthenia Gravis, Autoimmune, Experimental: immunology (MeSH) ; Receptors, Chimeric Antigen: immunology (MeSH) ; Receptors, Chimeric Antigen: genetics (MeSH) ; Neuromuscular Junction: immunology (MeSH) ; Autoantibodies ; Receptors, Cholinergic ; Receptors, Nicotinic ; Receptors, Chimeric Antigen

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)
2. Network Dysfunction (AG Schmitz)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

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