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Early clinical evidence from case reports, small case series, and early\u2010phase trials suggests that CD19\u2010 or BCMA\u2010directed CAR\u2010T cells can induce deep B\u2010cell or plasma\u2010cell depletion and sustained remission in selected patients with refractory autoimmune diseases; however, their comparative efficacy, durability, and long\u2010term safety remain incompletely defined. By contrast, CAR\u2010based treatment of organ fibrosis remains predominantly preclinical. In animal models, transient in vivo CAR\u2010T generation has attenuated fibrosis, whereas CAR\u2010macrophage(CAR\u2010M) approaches have demonstrated targeted phagocytosis and microenvironmental remodeling. Evidence for CAR\u2010natural killer cells (CAR\u2010NK) in non\u2010oncological diseases is currently limited to preclinical studies and an individual\u2010patient observation, despite their potential advantages for allogeneic and off\u2010the\u2010shelf manufacturing. This Review critically compares CAR\u2010T, CAR\u2010M, and CAR\u2010NK platforms, examines emerging unconventional immune\u2010cell and iPSC\u2010derived products, and evaluates programmable and in vivo CAR\u2010engineering strategies. We propose \u201ccontrollable spatiotemporal reprogramming\u201d as a framework linking target specificity, tissue distribution, activity duration, reversibility, manufacturing, and disease\u2010specific safety requirements.<\/jats:p>","DOI":"10.1002\/advs.77503","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:02:36Z","timestamp":1788141756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CAR\u2010Engineered Cell Therapies Beyond Cancer: Reprogramming Fibrosis and Immune\u2010Mediated Inflammation"],"prefix":"10.1002","volume":"13","author":[{"given":"Peng Jun","family":"Xu","sequence":"first","affiliation":[{"name":"The Nanomedicine Research Laboratory Hand Surgery Research Center Research Central of Clinical Medicine Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Affiliated Lianyungang Clinical College of Nantong University  Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-232X","authenticated-orcid":false,"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Rehabilitation Medicine Department of Rehabilitation Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"The Nanomedicine Research Laboratory Hand Surgery Research Center Research Central of Clinical Medicine Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya Xin","family":"Gu","sequence":"additional","affiliation":[{"name":"The Nanomedicine Research Laboratory Hand Surgery Research Center Research Central of Clinical Medicine Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"The Nanomedicine Research Laboratory Hand Surgery Research Center Research Central of Clinical Medicine Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-974X","authenticated-orcid":false,"given":"You Lang","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Nanomedicine Research Laboratory Hand Surgery Research Center Research Central of Clinical Medicine Affiliated Hospital of Nantong University Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e21776"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2025.03.004"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70306"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93557"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00590-z"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60954-X"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00720-1"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01070-3"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2.6.803"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02327-z"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1675807"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02269-w"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-020-00241-3"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910511"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.07.013"},{"key":"e_1_2_13_17_1","doi-asserted-by":"crossref","unstructured":"R.Vishnupriya T.Dhasneem F.Arfuso A. 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