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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.<\/jats:p>","DOI":"10.1038\/s41392-026-02783-5","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:02:38Z","timestamp":1790809358000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases"],"prefix":"10.1038","volume":"11","author":[{"given":"Zhuolin","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-8505","authenticated-orcid":false,"given":"Ningqiang","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-9720","authenticated-orcid":false,"given":"Xuexin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2783_CR1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/sj.leu.2403302","volume":"18","author":"C Imai","year":"2004","unstructured":"Imai, C. et al. 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