Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a transformative immunotherapeutic strategy with groundbreaking success in B-cell malignancies. In recent years, this powerful approach has been rapidly extended to autoimmune diseases, where autoreactive B cells play a central pathogenic role by producing autoantibodies, presenting autoantigens, and promoting chronic inflammation. Conventional treatments, including immunosuppressants and B-cell-depleting antibodies, often fail to induce sustained remission in refractory cases due to incomplete elimination of pathological B cells in lymphoid organs and inflamed tissues. This review comprehensively summarizes the structural design, generational evolution, clinical workflow, safety profiles, recent advances, and remaining challenges of CAR-T therapy for autoimmune diseases. CAR-T cells are engineered to target B-cell-restricted antigens such as CD19, CD20, and CD22 in an MHC independent manner, enabling specific and efficient clearance of autoreactive B cells. To date, five generations of CAR constructs have been developed, and fifth-generation universal allogeneic CAR-T cells represent a major breakthrough by offering offtheshelf availability, reduced manufacturing time, and lower costs. The standard clinical pipeline encompasses patient eligibility assessment, apheresis, T-cell isolation and genetic modification, ex vivo expansion, lymphodepletion chemotherapy, CAR-T infusion, intensive monitoring for adverse events, efficacy evaluation, and long-term follow-up. The primary adverse reactions are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are mostly manageable with timely intervention. Promising clinical data have demonstrated that CD19-targeted CAR-T therapy can induce durable drug-free remission in refractory systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis. Nevertheless, several critical challenges persist, including impaired quantity and function of autologous T cells in heavily pretreated patients, potential amplification of autoreactive T-cell clones, high production costs, and insufficient long-term safety and efficacy data. Future investigations should focus on optimizing CAR structure, developing safer universal cell products, establishing standardized protocols, and conducting large-scale multi-center clinical trials to advance CAR-T therapy into a mainstream curative option for refractory autoimmune diseases.
ZHANG et al. (Mon,) studied this question.