CAR-T Cell Therapy for Multiple Sclerosis: A Systematic Review of Emerging Clinical, Safety, and Biomarker Evidence
Daniel De Siqueira Lima1, Jose Felipe Lacerda Fernandes2, Luiza Alves Monteiro Torreão Villarim3, Arthur Felipe Barbosa Vasconcelos3, BIANCA ETELVINA OLIVEIRA3
1Psychiatry, UCSD, 2UNIPE, 3CREMPB
Objective:
To systematically evaluate the efficacy, safety, and biomarker effects of chimeric antigen receptor (CAR) T-cell therapy in multiple sclerosis (MS).
Background:
Current MS disease-modifying therapies are immunomodulatory and seldom induce deep or durable remission. The success of anti-CD20 monoclonal antibodies has highlighted B-cell depletion as an effective strategy. CAR-T cells engineered to target CD19 or autoreactive T-cell receptors may provide sustained immune reset and durable disease control.
Design/Methods:
A systematic review was performed according to PRISMA guidelines, including published case reports, case series, and early-phase clinical trials up to October 2025. Eligible studies reported outcomes of CD19- or peptide–MHC–directed CAR-T therapy in MS. Data extracted included demographics, CAR design, adverse events, MRI and clinical outcomes, and relapse-free survival. Risk of bias was assessed using the ROBINS-I tool.
Results:
Seventeen publications (N=27 patients) met inclusion criteria. Most patients had highly active or progressive MS refractory to conventional therapies. Universal B-cell depletion was achieved. Low-grade cytokine release syndrome occurred in approximately 30% of patients; no grade ≥3 neurotoxicity was reported. Among 13 patients who followed ≥6 months, 11 achieved “no evidence of disease activity” (NEDA). Cerebrospinal fluid neurofilament light chain levels decreased after treatment, supporting a biologic effect. However, all available studies were uncontrolled, heterogeneous, and at serious risk of bias.
Conclusions:
Early reports suggest CAR-T-cell therapy can induce prolonged remission in treatment-refractory MS with manageable short-term toxicity. Nonetheless, evidence remains preliminary, limited by small sample sizes and publication bias. Long-term safety—particularly persistent hypogammaglobulinemia, infection risk, and secondary malignancies—remains uncertain. Controlled trials with extended follow-up are essential to define the true therapeutic potential and safety profile of CAR-T therapy in MS.
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