Chimeric antigen receptor T-cell therapy in rheumatoid arthritis

Chimeric antigen receptor T-cell (CAR-T) therapy, previously used primarily in oncology, is emerging as a promising immunomodulatory strategy for rheumatoid arthritis. Its mechanism of action is based on T-cell engineering, enabling the selective elimination of autoreactive B cells, long-lived plasma cells, and other effector populations that sustain chronic inflammation. The most advanced constructs (including CD19-directed CAR-T therapy, B-cell maturation antigen-directed CAR-T therapy, and modular anti-fluorescein isothiocyanate CAR-T therapy) demonstrate the ability to achieve profound and sustained depletion of pathogenic immune cells, reduce proinflammatory cytokine levels, and induce remission in patients refractory to biological therapies. Advances in the design of subsequent generations of CARs, together with safety-enhancing technologies such as inducible caspase-9, herpes simplex virus thymidine kinase, and monoclonal antibody-based safety switches, have significantly improved control of adoptive lymphocyte activity and reduced the risk of cytokine release syndrome and persistent immunosuppression. However, therapeutic efficacy depends on multiple immunological factors, including the anticitrullinated protein antibody status, cytokine profile, and the functional reserve of T cells used for genetic modification. Preclinical evidence and early clinical observations suggest that CAR-T therapy may represent a new class of disease-modifying treatment for rheumatoid arthritis, with the potential to achieve durable remission and inhibit joint destruction. Nevertheless, further well controlled studies are required to optimize target selection, establish long-term safety, and define how this technology can be effectively integrated with existing therapeutic strategies. SIGNIFICANCE STATEMENT: This article discusses the possibility of a new application of chimeric antigen receptor T-cell (CAR-T) therapy in the treatment of patients with rheumatoid arthritis (RA). CAR-T therapy represents a novel approach for treatment of autoimmune diseases, including RA. Originally developed for hematological malignancies, this technology involves genetic modification of T cells to enable specific recognition and elimination of autoreactive B cells. Recently, increasing research into CAR-T therapy for RA has highlighted both substantial therapeutic potential and important safety concerns.