DOI: 10.4103/nrr.nrr-d-26-00089 ISSN: 1673-5374

Chimeric antigen receptor–based cell therapies for neuroimmune disorders: Therapeutic advances and structured standard treatment models

Yue Su, Xuan Che, Zhe Ruan, Fan Ning, Qiang Liu, Ting Chang

Chimeric antigen receptor-engineered cell therapies provide a novel therapeutic approach for refractory neuroimmune disorders. These cell products penetrate deep into tissue and achieve long-term depletion of pathogenic B cells and plasma cells, supporting sustained immune tolerance and durable clinical remission. Chimeric antigen receptor-T cells, chimeric antigen receptor-natural killer cells, chimeric autoantigen receptor T cells, and chimeric antigen receptor-regulatory T cells selectively target and eliminate pathological immune effectors, reduce autoantibody levels, and help maintain long-term remission in multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorder, chronic inflammatory demyelinating polyneuropathy, and autoimmune encephalitis. This review summarizes the therapeutic advance of chimeric antigen receptor-based cell therapies for neuroimmune disorders. Growing clinical evidence indicates that CD19-directed and B-cell maturation antigen-directed chimeric antigen receptor-T cells provide rapid and persistent clinical improvement even in patients with multiple prior treatment failures, accompanied by depletion of the B-cell lineage and sustained reduction in autoantibody titers. Key mechanisms include enhanced access across the blood-brain barrier, targeted lysis of tissue-resident memory B cells and long-lived plasma cells, and subsequent immune repertoire reconstitution. Important challenges remain incompletely defined, including long-term safety, late relapse, high manufacturing expenses, and restricted availability of autologous cell products. Further advances will require optimized chimeric antigen receptor architectures, off-the-shelf allogeneic platforms, and validation in large controlled clinical trials. This review presents a structured framework for future progress and highlights chimeric antigen receptor based immunotherapy as a pivotal strategy that replaces long term immunosuppression with durable drug free remission, thus reshaping the standard treatment model and redefining therapeutic goals for patients with neuroimmune disorders.

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