Chimeric antigen receptor T cells in autoimmune diseases and allergy: From bench to bedside

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B-cell malignancies and has attracted growing interest for autoimmune and allergic diseases. Because these disorders are often driven by pathogenic B cells that produce autoantibodies or allergen-specific IgE, they represent promising targets for CAR-T–based therapies. Studies have demonstrated that CD19-targeted CAR-T cells can induce deep and sustained drug-free remissions in severe autoimmune diseases, including systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis. Early evidence from multiple independent centers now extending to 36 months of follow-up indicates that CAR-T therapy may enable long-term disease control and potentially curative outcomes in carefully selected patients, rather than merely alleviating symptoms. Concurrently, preclinical research is advancing CAR-T approaches for allergic diseases, with efforts focused on eliminating IgE-producing B cells and engineering regulatory CAR-T cells to restore immune tolerance. In this review, we synthesized the mechanisms underlying CAR-T function, along with emerging preclinical data and clinical outcomes supporting its use in immune-mediated disorders. We also explored innovative strategies, including chimeric autoantibody receptor (CAAR) T cells, dual-targeting constructs, and next-generation CAR designs incorporating safety switches to improve efficacy and minimize toxicity. Despite promising early results, several challenges remain, including limited long-term safety data, the need for standardized patient selection criteria, manufacturing complexity, and questions regarding optimal timing and disease stage for intervention. Continued advances in cell engineering and scalable production are expected to address these limitations. Overall, CAR-T therapy represents a promising and potentially transformative approach for treating refractory autoimmune and allergic diseases.

Keywords

CAR-T cells / autoimmune diseases / systemic lupus erythematosus / allergy / B-cell depletion / regulatory T cells / immunotherapy / chimeric autoantibody receptor

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