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Despite advances in immunosuppressive therapy, a subset of patients develops treatment-resistant or refractory manifestations; terms used variably in the literature to describe inadequate response to multiple standard immunosuppressants. Chimeric antigen receptor T cell (CAR-T) therapy, a revolutionary modality in oncology, is now emerging as a promising approach in severe autoimmune diseases including SLE. By redirecting autologous T cells to target B cell antigens such as CD19 or BCMA, CAR-T therapy enables deep and sustained B cell depletion, potentially resetting immune tolerance.Early case series have reported encouraging remission rates and serologic improvements in refractory SLE; however, these observations derive from small, uncontrolled studies. The long-term durability, relapse risk, safety profile, and cost-effectiveness of CAR-T therapy in autoimmune disease remain uncertain and require confirmation in larger, controlled trials. This narrative review synthesizes the current understanding of CAR-T therapy in SLE, covering immunopathogenesis, rationale for B cell targeting, CAR-T mechanisms, preclinical evidence, clinical outcomes, safety considerations, and future directions. We integrate data from peer-reviewed studies, conference abstracts, and preprints up to August 2025, and propose a framework for integrating CAR-T into the treatment paradigm for refractory SLE.<\/jats:p>","DOI":"10.1007\/s12016-025-09114-6","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T12:20:23Z","timestamp":1764246023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Chimeric Antigen Receptor T Cell Therapy in Systemic Lupus Erythematosus: Mechanisms, Clinical Advances, and Future Directions a Comprehensive Review"],"prefix":"10.1007","volume":"68","author":[{"given":"Ahmad","family":"Matarneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayan","family":"Matarneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Salameh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrauof","family":"Akkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrollah","family":"Ghahramani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naman","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"issue":"5","key":"9114_CR1","doi-asserted-by":"publisher","first-page":"825","DOI":"10.2215\/CJN.05780616","volume":"12","author":"S Almaani","year":"2017","unstructured":"Almaani S, Meara A, Rovin BH (2017) Update on lupus nephritis. 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