CAR-T-cell therapy for autoimmune neurologic diseases

Autoimmune neurologic diseases include multiple sclerosis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune encephalitis, myasthenia gravis, stiff-person syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and related syndromes. The contributions of B cells, plasma cells, and autoantibodies differ substantially across these disorders; however, the B-cell lineage represents a therapeutically actionable target in many of them. Chimeric antigen receptor T-cell therapy, originally developed for hematologic malignancies, offers a potential strategy for deep and potentially durable depletion of pathogenic B-lineage cells and subsequent immune reconstitution. In recent years, CD19, BCMA, dual-target, mRNA CAR-T-cell, and chimeric autoantibody receptor T-cell approaches have generated preliminary clinical or translational evidence, primarily in systemic autoimmune diseases. Clinical evidence in neurologic disorders remains limited and spans myasthenia gravis, NMOSD, MOGAD, multiple sclerosis, autoimmune encephalitis, stiff-person syndrome, and CIDP. This review summarizes the biologic rationale, disease-specific evidence, target selection, safety concerns, and trial-design considerations for CAR-T-cell therapy in autoimmune neurologic diseases. Current evidence supports further investigation of CAR-T cells in selected patients with highly refractory, antibody- or B-cell-driven neuroimmune disorders, but does not establish superiority over existing therapies. However, the field remains dominated by case reports and small early-phase studies, with randomized evidence currently confined to one phase 2b trial in myasthenia gravis. Establishing the risk-benefit profile will require stringent patient selection, disease-specific neurologic monitoring, controlled prospective studies, and long-term follow-up.