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Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells

Item Type:Article
Title:Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells
Creators Name:Reincke, S.M. and von Wardenburg, N. and Homeyer, M.A. and Kornau, H.C. and Spagni, G. and Li, L.Y. and Kreye, J. and Sánchez-Sendín, E. and Blumenau, S. and Stappert, D. and Radbruch, H. and Hauser, A.E. and Künkele, A. and Edes, I. and Schmitz, D. and Prüss, H.
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.
Keywords:CAAR T Cell, Autoimmunity, Cell Therapy, NMDA Receptor Encephalitis, Autoimmune Encephalitis, Chimeric Autoantibody Receptor, T Cells, Animals, Mice
Publisher:Cell Press
Page Range:5084-5097.e18
Date:9 November 2023
Official Publication:https://doi.org/10.1016/j.cell.2023.10.001
PubMed:View item in PubMed

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