{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:01:30Z","timestamp":1789052490703,"version":"build-2803163510"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chimeric antigen receptor T-cell (CAR-T) therapy has expanded beyond oncology and is emerging as a promising strategy for autoimmune diseases. Early clinical experience, particularly with CD19-directed CAR-T cells, has shown that deep remission can occur in refractory disorders such as systemic lupus erythematosus, inflammatory myopathies, and systemic sclerosis. These observations are consistent with an immune-reset-like process, although its durability, cellular basis, and disease-specific mechanisms remain incompletely defined. However, the clinical development landscape remains uneven. Based on an April 2026 Trialtrove snapshot, the field is growing rapidly but remains concentrated in a limited number of countries, diseases, and target classes, with most studies in early-phase development. These features suggest that autoimmune CAR-T therapy has moved beyond proof of concept, but has not yet reached a mature, indication-optimized stage of clinical translation. In this Perspective, we argue that the next phase of progress will depend less on increasing trial numbers than on improving biological precision, platform diversity, and trial design. The current pipeline is dominated by CD19-centered programs and diseases in which B-cell depletion appears biologically plausible, but this approach is unlikely to be equally informative across autoimmune disease. Key questions remain regarding remission durability, relapse after B-cell reconstitution, patient selection, toxicity management, and scalability. Looking ahead, major opportunities include plasma cell-directed approaches, dual-target strategies, chimeric autoantigen receptor platforms, tolerance-oriented cell therapies, off-the-shelf products, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    engineering. The near-term readout window will be critical in determining whether autoimmune CAR-T therapy becomes broadly deployable or remains limited to selected indications and settings.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1853170","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:07:57Z","timestamp":1780034877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CAR-T cell therapy for autoimmune diseases: current clinical trial landscape and the next wave of development"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingyu","family":"Chen","sequence":"first","affiliation":[{"name":"The Second School of Medicine, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Second School of Medicine, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqi","family":"Xu","sequence":"additional","affiliation":[{"name":"The First School of Medicine, School of Information and Engineering, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yemeng","family":"He","sequence":"additional","affiliation":[{"name":"Renji College of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine and Life Sciences, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Nursing and Midwifery, University of Galway","place":["Galway, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101039","DOI":"10.1016\/j.medj.2026.101039","article-title":"Anti-CD19 CAR T cell therapy for refractory SLE-ITP","volume":"7","author":"Li","year":"2026","journal-title":"Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5","article-title":"Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus","volume":"28","author":"Mackensen","year":"2022","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"CD19 CAR T-cell therapy in autoimmune disease - A case series with follow-up","volume":"390","author":"M\u00fcller","year":"2024","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-223952","article-title":"Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells","volume":"82","author":"Bergmann","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04170-z","article-title":"BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: exploratory biomarker analysis of a placebo-controlled phase 2b trial","volume":"32","author":"Fedak","year":"2026","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s40291-024-00730-0","article-title":"The future of CAR T therapeutics to treat autoimmune disorders","volume":"28","author":"Pecher","year":"2024","journal-title":"Mol Diagn Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2025.101354","article-title":"CARing about autoimmune disorders. 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