CAR T-cell therapy in autoimmune diseases: Opportunities and challenges, with implications for RA.

Chimeric antigen receptor (CAR) T-cell therapy, initially developed for hematologic malignancies, is now being applied to autoimmune diseases. This review examines CAR T-cell applications in autoimmunity, focusing on rheumatoid arthritis (RA). We analyze CAR T-cell technology development, generational evolution, and manufacturing considerations. Clinical trials in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and other autoimmune conditions demonstrate that single CAR T-cell infusions induce sustained, drug-free remission through selective pathogenic B-cell depletion and immune tolerance restoration. RA presents distinct challenges: disease heterogeneity, multi-cellular involvement (autoreactive T/B cells, synovial fibroblasts), and absence of universal target antigens. Preclinical approaches include HLA-DR1-targeted CARs for autoreactive CD4 + T cells and anti-FITC CARs for citrullinated peptide-specific B cells, though clinical optimization remains necessary. RA requires higher therapeutic precision than other autoimmune diseases due to established effective conventional treatments. Advances in allogeneic CAR T cells, dual-targeting constructs, and safety mechanisms (suicide switches) may facilitate clinical implementation. This review evaluates CAR T-cell therapy potential in autoimmune disease treatment and RA-specific therapeutic challenges.