Current status and future prospects of CAR-T therapy for autoimmune diseases

Chimeric antigen receptor T-cell (CAR-T) therapy, originally developed for B-cell malignancies, is rapidly being repurposed for severe systemic autoimmune rheumatic diseases. The rationale extends beyond suppression of autoantibody production, as B cells also function as antigen-presenting cells, cytokine producers, and organizers of pathogenic immune interactions. CD19-directed CAR-T cells can achieve broader and deeper B-cell depletion than conventional antibody-based approaches and may disrupt self-sustaining autoimmune networks. Early clinical experience across systemic autoimmune diseases has shown striking responses, including drug-free remission in selected patients. Importantly, disease control may persist despite CAR-T contraction and subsequent B-cell reconstitution, supporting the concept of an “immune reset,” although this should not be equated with cure. In autoimmune diseases, long-term CAR persistence may not be required, and toxicity profiles and therapeutic goals differ from those in hematologic malignancies. Meanwhile, clinical development is expanding beyond autologous CD19-directed CAR-T cells to BCMA-directed, dual-target, allogeneic, natural killer cell, induced pluripotent stem cell-derived, and in vivo CAR platforms. This review discusses the biological rationale, emerging clinical evidence, safety and management considerations, and future development of CAR-based cellular therapy for systemic autoimmune rheumatic diseases.