%0 Journal Article
%A Reincke, S Momsen
%A von Wardenburg, Niels
%A Homeyer, Marie A
%A Kornau, Hans-Christian
%A Spagni, Gregorio
%A Li, Lucie Y
%A Kreye, Jakob
%A Sánchez-Sendín, Elisa
%A Blumenau, Sonja
%A Stappert, Dominik
%A Radbruch, Helena
%A Hauser, Anja E
%A Künkele, Annette
%A Edes, Inan
%A Schmitz, Dietmar
%A Prüss, Harald
%T Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells.
%J Cell
%V 186
%N 23
%@ 0092-8674
%C New York, NY
%I Elsevier
%M DKFZ-2023-02252
%P 5084-5097.e18
%D 2023
%Z 2023 Nov 9;186(23):5084-5097.e18
%X 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.
%K CAAR T cell (Other)
%K NMDA receptor encephalitis (Other)
%K T cells (Other)
%K autoimmune encephalitis (Other)
%K autoimmunity (Other)
%K cell therapy (Other)
%K chimeric autoantibody receptor (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37918394
%R 10.1016/j.cell.2023.10.001
%U https://inrepo02.dkfz.de/record/285128