国产CAR-T细胞疗法，又双叒叕登上顶刊Cell：BCMA-CAR-T治疗进行性多发性硬化症

Core Insights - The article discusses the potential of anti-BCMA CAR-T cell therapy in treating progressive multiple sclerosis (PMS), highlighting its effectiveness and safety in clinical trials [4][11]. Group 1: Disease Overview - Progressive multiple sclerosis (PMS) is characterized by chronic inflammation in the central nervous system, leading to brain atrophy and demyelination [3]. - Current treatment options for PMS are limited and often ineffective, posing significant challenges for clinical management [3]. Group 2: Treatment Mechanism - B cells are identified as key drivers of disease progression through various mechanisms, including the production of autoantibodies and inflammatory cytokines [3]. - Existing B cell depletion therapies, such as CD20-targeted monoclonal antibodies, have shown efficacy in treating relapsing forms of multiple sclerosis but are limited in their ability to target plasma cells in the central nervous system due to the blood-brain barrier [3]. Group 3: Clinical Trial Findings - A phase 1 clinical trial involving 5 PMS patients (1 primary, 4 secondary) demonstrated that anti-BCMA CAR-T cell therapy is safe and effective [4]. - The therapy resulted in a significant reduction of plasma cells in the central nervous system and showed sustained expansion of CAR-T cells in cerebrospinal fluid, indicating a unique response in the CNS environment [6][9]. - Patients exhibited notable functional improvements over a follow-up period of up to 9 months, which was not observed in cases treated with anti-CD19 CAR-T cells [6][11]. Group 4: Safety Profile - The therapy was associated with only grade 1 cytokine release syndrome, and all grade 3 or higher cytopenias occurred within 40 days post-infusion [7]. Group 5: Future Implications - The study provides insights into the potential application of anti-BCMA CAR-T cell therapy in clinical management of PMS and suggests further research to evaluate long-term clinical efficacy and durability of treatment [11].