Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases

Abstract The application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies has driven significant advancements in this form of immunotherapy. The therapeutic strategy of CAR-T cells targeting specific cell populations has opened new avenues for treating non-oncological diseases, such as autoimmune diseases, aging-related conditions, and infections. For instance, in non-oncological diseases like systemic lupus erythematosus (SLE), abnormal B cell development or dysfunction leads to the production of autoantibodies, triggering localized deposition of immune complexes and resulting in tissue or organ damage and dysfunction. Relevant studies have identified disease-specific surface antigens or pathogenic cell subsets, making CAR-T cell therapy a feasible treatment approach. Moreover, in non-oncological diseases, CAR-T cells can mediate immune remodeling for certain conditions, thereby achieving long-term therapeutic remission. Although no CAR-T therapies have yet been approved for non-oncological diseases, multiple clinical trials have been initiated, with some achieving interim successes (e.g., allogeneic CAR-T cells have demonstrated efficacy in treating rheumatic diseases). Meanwhile, ongoing research into the pathogenesis of non-neoplastic diseases further supports the potential application of CAR-T cells. With this background, this article aims to introduce the latest research, mechanisms, and applications of CAR-T cell therapy in non-oncological diseases, summarize the pathogenesis of related disorders, and discuss the advantages, challenges, and future prospects of CAR-T cell therapy.