The Evolving Landscape of CAR T-Cell Therapy in Autoimmune Diseases: A State-of-the-Art Review (2025).

Autoimmune diseases, characterized by a breakdown in immune tolerance and persistent autoantibody production, have traditionally been managed primarily through broad-spectrum immunosuppression. Chimeric antigen receptor (CAR) T-cell therapy, a groundbreaking modality once exclusive to oncology, has recently emerged as a transformative approach for treating autoimmunity. We conducted a comprehensive review and investigation into the applications of CAR T-cell therapy in distinct autoimmune diseases, mainly rheumatic diseases, exploring the full spectrum of CAR T modalities, including autologous, allogeneic, and the latest in vivo CAR T strategies. By combining preclinical studies with clinical evidence, we aim to elucidate the substantial potential of CAR T cells to achieve drug-free remission in autoimmune disorders through deep depletion of B cells and immune reset. Despite these promising outcomes from small cohorts or case studies, significant hurdles remain in the realms of safety and toxicity management, economic burden, complex manufacturing processes, and accessibility. In summary, this cross-disease and cross-platform review has thoroughly examined the current state of CAR T-cell therapy research for autoimmune diseases up to December 2025, providing updated insights and future perspectives on this transformative therapeutic strategy.