Recent developments in chimeric antigen receptor (CAR) T-cell therapy have shown potential in treating progressive forms of multiple sclerosis (MS). Researchers are exploring the use of engineered T cells to target and eliminate autoreactive B cells, which play a significant role in the immune system's attack on the central nervous system. A new investigational treatment, BMS-986354, is currently undergoing clinical trials. Early data presented at the 2025 ACTRIMS Forum indicate promising initial safety and efficacy results, with no reports of immune effector cell-associated neurotoxicity syndrome (ICANS).

Understanding the Mechanism Behind BMS-986354

The innovative approach of BMS-986354 involves using engineered T cells to combat MS by targeting autoreactive B cells. This method leverages the success seen in CAR T-cell therapies for treating cancers like lymphoma and leukemia. The therapy aims to selectively destroy harmful B cells that contribute to the immune system’s misdirected attacks on the central nervous system. Initial findings suggest that this targeted approach can achieve robust T cell expansion and deep B cell depletion within a week of treatment.

Dr. Rosanna Ricafort, a senior global program lead at BMS, highlighted the mechanism behind BMS-986354 during an interview with NeurologyLive®. She explained that the therapy uses a next-generation manufacturing process to produce CD19-directed CAR T cells. These cells are designed to recognize and eliminate autoreactive B cells effectively. Early data from the phase 1 study show no dose-limiting adverse events, indicating a favorable safety profile. Moreover, the treatment achieved significant B cell depletion within eight days, aligning with expectations based on previous research.

Preliminary Findings and Future Prospects

Initial results from the ongoing phase 1 trial of BMS-986354 provide encouraging signs for its potential as a treatment for progressive or relapsing MS. The study has demonstrated promising safety outcomes, with no instances of ICANS reported among patients. Additionally, the therapy showed effective T cell expansion and rapid depletion of B cells, suggesting it could be a viable option for managing MS symptoms. While these findings are preliminary, they represent a significant step forward in the development of CAR T-cell therapies for autoimmune diseases.

The phase 1 trial involved administering a single infusion of BMS-986354 to patients following lymphodepletion. The dosing ranged from 5 x 10^6 CAR-positive T cells per patient. Data presented at the ACTRIMS Forum indicated that the treatment was well-tolerated, with no serious adverse events linked to the therapy. Dr. Ricafort emphasized that although the data are still early, they offer hope for patients with progressive MS. The absence of dose-limiting toxicities and the observed B cell depletion support the continued exploration of this promising therapeutic approach. Further studies will be crucial to validate these initial findings and assess long-term efficacy and safety.