[SMLE] Chimeric antigen receptor T cell therapy in autoimmune neurological disease: current status of efficacy and safet

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BMJ Neurol Open. 2026 Sep 29;8(2):e001611. doi: 10.1136/bmjno-2026-001611. eCollection 2026.

ABSTRACT

Autoimmune neurological diseases affecting the central nervous system, peripheral nervous system and neuromuscular junction are frequently refractory to conventional B-cell-depleting therapies such as CD20-directed monoclonal antibodies, highlighting a need for more effective treatment approaches. Chimeric antigen receptor T (CAR-T) cell therapy, initially developed for haematological malignancy, has been repurposed to more comprehensively deplete pathogenic B-cell and plasma cell populations in autoimmune disease, raising the possibility of durable, treatment-free remission. This scoping review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-ScR guidelines, examined published clinical studies from January 2023 to January 2026 in which CAR-T cells targeting CD19, CD20 or B-cell maturation antigen were used to treat autoimmune neurological disease, identifying 19 eligible studies. Efficacy signals were most consistent in refractory acetylcholine receptor antibody-positive generalised myasthenia gravis and Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, with encouraging but more preliminary results reported in multiple sclerosis, Lambert-Eaton myasthenic syndrome, myelin oligodendrocyte glycoprotein antibody-associated disease, chronic inflammatory demyelinating polyneuropathy, stiff-person syndrome and autoimmune encephalitis. Relapse was reported across several conditions, with follow-up generally limited to under two years. The safety profile compared favourably with that seen in oncological CAR-T use, with lower rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, although cytopenias, infection and prolonged hypogammaglobulinaemia remain clinically significant, and local immune effector cell-associated toxicity syndrome is an emerging concern not yet formally reported in this population. Current evidence remains limited to small, largely uncontrolled studies with heterogeneous outcome reporting. Adequately powered, longer-term controlled trials are needed before CAR-T therapy can be recommended more broadly in the management of refractory autoimmune neurological disease.

PMID:42824951 | PMC:PMC13630046 | DOI:10.1136/bmjno-2026-001611


Source: https://pubmed.ncbi.nlm.nih.gov/4282495 ... 9&v=2.20.1