Journal Article

DZNE-2023-01062

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells.

Reincke, M. (First author)DZNE* ; von-Wardenburg, N.-O.DZNE* ; Homeyer, M. A.DZNE* ; Kornau, H.-C.DZNE* ; Spagni, G.DZNE* ; Li, L. Y.DZNE* ; Kreye, J.DZNE* ; Sánchez-Sendín, E.DZNE* ; Blumenau, S.Extern* ; Stappert, D.DZNE* ; Radbruch, H. ; Hauser, A. E. ; Künkele, A. ; Edes, I. ; Schmitz, D.DZNE* ; Prüss, H. (Last author)DZNE*

2023
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2023.10.001

Abstract: Anti-NMDA receptor (NMDAR) autoantibodies cause NMDAR encephalitis, the most common autoimmune encephalitis, leading to psychosis, seizures, and autonomic dysfunction. Current treatments comprise broad immunosuppression or non-selective antibody removal. We developed NMDAR-specific chimeric autoantibody receptor (NMDAR-CAAR) T cells to selectively eliminate anti-NMDAR B cells and disease-causing autoantibodies. NMDAR-CAARs consist of an extracellular multi-subunit NMDAR autoantigen fused to intracellular 4-1BB/CD3ζ domains. NMDAR-CAAR T cells recognize a large panel of human patient-derived autoantibodies, release effector molecules, proliferate, and selectively kill antigen-specific target cell lines even in the presence of high autoantibody concentrations. In a passive transfer mouse model, NMDAR-CAAR T cells led to depletion of an anti-NMDAR B cell line and sustained reduction of autoantibody levels without notable off-target toxicity. Treatment of patients may reduce side effects, prevent relapses, and improve long-term prognosis. Our preclinical work paves the way for CAAR T cell phase I/II trials in NMDAR encephalitis and further autoantibody-mediated diseases.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Autoantibodies: metabolism (MeSH) ; Encephalitis: metabolism (MeSH) ; Encephalitis: therapy (MeSH) ; Receptors, N-Methyl-D-Aspartate (MeSH) ; T-Lymphocytes (MeSH) ; Autoimmune Diseases (MeSH) ; Disease Models, Animal (MeSH) ; CAAR T cell ; CAAR T cell ; CAAR T cell ; CAAR T cell ; CAAR T cell ; CAAR T cell ; NMDA receptor encephalitis ; T cells ; autoimmune encephalitis ; autoimmunity ; cell therapy ; chimeric autoantibody receptor ; Autoantibodies ; Receptors, N-Methyl-D-Aspartate

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)
2. Laboratory Automation Technologies (CRFS-LAT) (LAT)
3. 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)

Experiment(s):

1. Laboratory Automation Technologies (CRFS-LAT) / Bonn

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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