Chimeric antigen receptor T-cell therapy in systemic lupus erythematosus: From B cell depletion to immune reprogramming.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which current immunosuppressive and biologic therapies often fail to achieve durable remission in refractory patients. The emergence of chimeric antigen receptor T-cell (CAR-T) therapy has introduced a fundamentally new therapeutic concept, shifting therapeutic strategies from transient immune suppression toward the possibility of durable immune reprogramming. Recent studies suggest that the benefit of CAR-T therapy extends beyond depletion of autoreactive B cells. By depleting disease-associated immune cell populations and promoting immune reconstitution, CAR-T therapy may contribute to immune reprogramming, providing a potential biological basis for sustained treatment-free remission. In this review, we summarize the rapidly evolving landscape of CAR-based therapies for SLE, including conventional and next-generation strategies, and discuss their mechanisms, clinical efficacy, durability, and safety. We further highlight emerging approaches aimed at improving precision, accessibility, and long-term outcomes. Rather than serving solely as a B-cell-depleting therapy, CAR-T may represent a platform for immune reprogramming. Future advances in target selection, biomarker-guided patient stratification, and engineered cellular platforms may further improve the precision and durability of CAR-based therapies, with the long-term goal of achieving durable immune reprogramming and treatment-free remission.