Redefining multiple sclerosis with CAR-T cell therapy

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by aberrant immune responses against myelin and neuronal antigens, resulting in demyelination, axonal injury, and progressive neurological impairment. Although current immunomodulatory therapies can reduce relapse frequency and slow disease progression, they rarely induce durable remission or reverse established pathology. Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, initially developed for cancer treatment, has recently emerged as a promising strategy for autoimmune diseases. By engineering T cells to selectively eliminate autoreactive B cells or other pathogenic immune populations, CAR-T therapy holds the potential to achieve long-lasting disease control and even immune system reset. Preclinical studies and early-phase clinical trials targeting CD19⁺ B cells have shown encouraging efficacy in autoimmunity, including MS. Nonetheless, significant challenges remain, such as optimizing antigen targets, minimizing treatment-associated toxicities, sustaining therapeutic benefit, and advancing scalable, safe, and cost-effective clinical applications. In this review, we summarize recent advances in applying CAR-T cell therapy to MS, outline key lessons learned from oncology and other autoimmune diseases, and discuss future directions for establishing CAR-T cells as a transformative approach in neuroimmunology.