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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., Competing Interests: Declaration of interests Related to this work, the German Center for Neurodegenerative Diseases (DZNE) and Max-Delbrück-Centrum Berlin have filed a patent application describing NMDAR-CAAR T cells for treatment of NMDAR encephalitis on which S.M.R., I.E., and H.P. are named as inventors (WO/2020/245343). In addition, the DZNE has filed a patent application on constructs for detection and isolation of NMDAR autoantibodies on which H.-C.K. and H.P. are named as inventors (WO/2021/008890)., (Copyright © 2023 Elsevier Inc. All rights reserved.)