Chimeric antigen receptor T-cell therapy in neuroimmune diseases: mechanistic rationale, clinical experience, and translational challenges.

Authors

Yaqiao Yi, Hui Xiao, Yitong Yin, Rong Zeng, Qingqing Yan, Yonghe Wu, Kailin Yang, Guilong Fu, Hui Xu, Xiongmei Zhang

Published in

Frontiers in immunology. Volume 17. Pages 1913956. Epub Sep 16, 2026.

Abstract

Neuroimmune diseases comprise a heterogeneous group of disorders in which B cells, plasmablasts, plasma cells, autoantibodies, and T cells contribute differently to tissue injury. Although B-cell-directed biologics have improved disease control, some patients continue to experience treatment-refractory activity, relapse after treatment withdrawal, or cumulative neurological disability. Chimeric antigen receptor T-cell (CAR-T cell) therapy offers a means of achieving deeper and potentially sustained depletion of defined pathogenic immune-cell compartments. This narrative review integrates the mechanistic rationale, target selection, platform design, published human experience, and translational challenges of CAR-T cell therapy in neuroimmune diseases. Current strategies predominantly target CD19-expressing B-lineage cells or BCMA-expressing antibody-secreting cells; these therapeutic targets are distinct from disease autoantigens, and their relevance depends on the immunopathology of each disorder. CAR design, persistence, lymphodepletion, and the use of integrating or transient expression platforms further influence treatment activity and risk. Clinical development remains uneven across indications. Myasthenia gravis has the most diverse clinical experience, encompassing integrating CD19-, BCMA-, and dual CD19/BCMA-targeted products, together with a transient BCMA-targeted mRNA platform evaluated in a randomized, placebo-controlled phase 2b study. In neuromyelitis optica spectrum disorder, an open-label phase 1 study has demonstrated early clinical and immunological activity of BCMA-targeted CAR-T cells. Evidence in multiple sclerosis and stiff-person syndrome is derived from individual reports, small early-phase studies, and conference data, whereas experience in other neuroimmune diseases remains limited to isolated reports or small case series. Across indications, interpretation is constrained by small and heterogeneous cohorts, limited follow-up, and the predominance of uncontrolled observations. Major translational considerations include target breadth and selectivity, the contribution of lymphodepletion, the disease-dependent relevance of central nervous system trafficking, acute and delayed toxicity, patient selection, manufacturing feasibility, biomarker development, and standardized long-term outcome assessment. CAR-T cell therapy has shown preliminary clinical activity in selected patients with refractory neuroimmune diseases, but its comparative efficacy, durability, and long-term safety remain undefined. It therefore remains investigational for most neuroimmune indications.

PMID:
42819529
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.