Chimeric Antigen Receptor T-cell (CAR-T) Therapy in Autoimmune Diseases: A Narrative Review

Abstract

Autoimmune diseases are chronic immune-mediated disorders that, in their systemic forms, such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), remain associated with progressive organ damage, impaired quality of life, and excess mortality despite conventional immunosuppression. A substantial proportion of patients experience refractory disease, recurrent flares, and glucocorticoid dependence, underscoring the need for therapies that address the underlying disease process rather than merely suppressing symptoms. Chimeric antigen receptor T-cell (CAR-T) therapy, originally developed for B-cell malignancies, has emerged as a potential paradigm shift by achieving deep, tissue-level B-cell depletion followed by immune reconstitution, a process often described as an "immune reset." This narrative review summarizes the immunological rationale, clinical evidence, safety profile, and future directions of B-cell-directed (anti-CD19) CAR-T therapy in autoimmune disease. Current evidence identifies refractory SLE as the most mature indication, with reproducible drug-free remission, seroconversion, and durable responses across independent cohorts. Early studies in inflammatory myopathies and SSc report encouraging responses and reduced immunosuppressive requirements, whereas evidence in AAV remains preclinical. Toxicities such as cytokine release syndrome and neurotoxicity appear less frequent and less severe than in oncology, although infections and hypogammaglobulinemia require monitoring. High cost, complex manufacturing, and limited long-term data remain major barriers, while allogeneic CAR-natural killer cells and in vivo engineering may improve scalability. Larger controlled studies with longer follow-up are needed before routine clinical use.