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Key challenges include shared surface antigen expression among CAR-T cells, normal T cells, and malignant T cells, leading to fratricide and T-cell aplasia, and the risk of tumor cell contamination during CAR-T manufacturing. This review summarizes recent advances in CAR-based therapies for T-cell malignancies, focusing on clinical translation barriers, emerging solutions, and future directions. We highlight promising target antigens under preclinical and clinical investigation, as well as alternative effector platforms, including natural killer (NK) cells, NKT cells, \u03b3\u03b4 T cells, and macrophages, that hold potential as next-generation CAR-expressing cellular therapeutics.<\/jats:p>","DOI":"10.1093\/cei\/uxag060","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:38:54Z","timestamp":1791027534000},"source":"Crossref","is-referenced-by-count":0,"title":["Precision targeting and alternative effector cells: revolutionizing CAR-based therapy for T-cell malignancies"],"prefix":"10.1093","volume":"220","author":[{"given":"Yingtong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hematology, Lymphoma Research Center, Peking University Third Hospital , Haidian District, Beijing \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Lymphoma Research Center, Peking University Third Hospital , Haidian District, Beijing \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuozi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Lymphoma Research Center, Peking University Third Hospital , Haidian District, Beijing \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Lymphoma Research Center, Peking University Third Hospital , Haidian District, Beijing \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4958-2489","authenticated-orcid":false,"given":"Hongmei","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Hematology, Lymphoma Research Center, Peking University Third Hospital , Haidian District, Beijing \u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"2026102211180192300_uxag060-B1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"2026102211180192300_uxag060-B2","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1016\/S1470-2045(19)30031-2","article-title":"Comparative 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