CAR-T cell therapy for autoimmune diseases: from immune suppression to immune resetting.
Autoimmune diseases are heterogeneous disorders marked by immune dysregulation, loss of self-tolerance, autoantibody production, and chronic inflammation. Although immunosuppressants and biologics have improved disease control, incomplete remission, relapse after withdrawal, cumulative toxicity, and failure to restore immune homeostasis remain common. Chimeric antigen receptor T-cell (CAR-T) therapy offers a potential strategy for refractory autoimmune diseases by selectively eliminating pathogenic immune compartments and providing a theoretical pathway toward target-dependent immune remodeling and immune resetting. This review summarizes immunopathogenesis and therapeutic gaps in representative autoimmune diseases, compares CAR-T applications in malignancies and autoimmunity, and evaluates emerging response endpoints, target-selection strategies, and safety considerations in autoimmune settings. Early clinical evidence suggests rapid disease control, autoantibody reduction, and immunosuppression-free remission in selected B-cell- or autoantibody-driven diseases. However, reported remission duration and response proportions remain limited by small cohorts, short follow-up, and disease-specific heterogeneity. The central unresolved question is whether durable remission can be achieved without persistent immune deficiency. Cytokine release syndrome, infection, hypogammaglobulinemia, relapse, impaired vaccine responses, T-cell fitness, manufacturing barriers, and cost remain key challenges. Future studies should define optimal targets, standardized remission endpoints, durable remission biomarkers, long-term safety, and the role of T-cell engagers.