Challenges and opportunities: CAR-T cell therapy in autoimmune diseases

Chimeric antigen receptor T (CAR-T) cell therapy is rapidly moving from hematologic malignancies into severe autoimmune disease, particularly B cell-mediated disorders such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and inflammatory myopathies. Recent autologous and allogeneic studies show that deep immune-cell depletion can induce drug-free remission or major clinical responses in the refractory patients. However, translating CAR-T cell therapy into autoimmune disease raises challenges that differ from oncology, including target selection in heterogeneous immune ecosystems, depletion of nonpathogenic immune compartments, control of cytokine release syndrome and infection risk, definition of the optimal degree of CAR persistence, and scalable manufacturing. In this review, we summarize the major obstacles and emerging opportunities for CAR-T cell therapy in autoimmune diseases, with emphasis on representative clinical studies, candidate targets beyond CD19, engineering strategies to improve safety and durability, and the specific promise and limitations of allogeneic platforms.