{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:21Z","timestamp":1789409601711,"version":"build-2803163510"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U23A20453,82270223,82170209,82350109"],"award-info":[{"award-number":["U23A20453,82270223,82170209,82350109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Anhui Provincial Department of Education Scientific Research Project","award":["2023AH010079"],"award-info":[{"award-number":["2023AH010079"]}]},{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2308085J09"],"award-info":[{"award-number":["2308085J09"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"crossref"}]},{"name":"USTC Research Funds of the Double First-Class Initiative","award":["YD9110002047"],"award-info":[{"award-number":["YD9110002047"]}]},{"name":"International Cooperation Projects in Anhui Province","award":["2023h11020005"],"award-info":[{"award-number":["2023h11020005"]}]},{"name":"Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM","award":["2025IHM01080"],"award-info":[{"award-number":["2025IHM01080"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>Ex vivo engineering strategies for adoptive \u03b1\u03b2 T cell therapies increasingly use pharmacological modulation to improve survival, expansion, and antitumor activity. Short-term exposure to the B cell lymphoma-2 (BCL-2) inhibitor venetoclax during \u03b1\u03b2 T cell manufacturing enhances apoptotic priming and effector persistence, suggesting a route to strengthen other T cell lineages. \u03b3\u03b4 T cells share cytotoxic properties with \u03b1\u03b2 T cells but recognize targets independently of major histocompatibility complex and show low alloreactivity, supporting off-the-shelf use in acute myeloid leukemia (AML). Whether such conditioning benefits \u03b3\u03b4 T cells was unknown. Here, we show that ex vivo venetoclax pretreatment enhances the antileukemic efficacy of therapeutic \u03b3\u03b4 T cells and chimeric antigen receptor (CAR) \u03b3\u03b4 T cells. Venetoclax-pretreated \u03b3\u03b4 T cells displayed increased cytotoxicity and proliferation with reduced exhaustion, yielding superior control of AML blasts and xenografts. These functional gains coincided with elevated mitochondrial content and a fatty acid oxidation metabolic profile. In vivo, venetoclax-pretreated \u03b3\u03b4 T cells achieved durable disease suppression, and the same conditioning improved CAR \u03b3\u03b4 T cell efficacy. Together, these results show that short-term BCL-2 inhibition enhances \u03b3\u03b4 T cell cytotoxicity and persistence. Incorporating venetoclax pretreatment into \u03b3\u03b4 T cell manufacturing may improve therapeutic efficacy and inform next-generation \u03b3\u03b4 T cell therapies for AML.<\/jats:p>","DOI":"10.1172\/jci202932","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:00:17Z","timestamp":1784822417000},"source":"Crossref","is-referenced-by-count":0,"title":["Ex vivo pretreatment with venetoclax boosts antileukemic efficacy of therapeutic \u03b3\u03b4 T cells in AML models"],"prefix":"10.1172","volume":"136","author":[{"given":"Xingchi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hematology, Centre for Leading Medicine and Advanced Technologies of IHM, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, and"},{"name":"Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China."},{"name":"Anhui Provincial Key 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