{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:00:11Z","timestamp":1790658011562,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2025NSFJQ0057"],"award-info":[{"award-number":["2025NSFJQ0057"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2026NSFSC0124"],"award-info":[{"award-number":["2026NSFSC0124"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Senolytic CAR\u2010T cells targeting uPAR induce dose\u2010dependent toxicities. Although dosage adjustment mitigates these toxicities in laboratory mice, clinical translation remains challenging owing to the unpredictability of CAR\u2010T cell proliferation across heterogeneous patient populations. In contrast, bispecific T\u2010cell engagers (BiTEs) offer a safer alternative with superior dose\u2010titratability. Here, we have developed a GFD\u2010CD3 BiTE by employing the growth factor\u2010like domain (GFD) of the natural ligand uPA as the targeting moiety to target uPAR\u2010positive senescent cells. Dose\u2010range finding studies revealed that high\u2010dose GFD\u2010CD3 predominantly induced hepatotoxicity through T cell\u2013mediated attack on hepatic endothelial cells. Crucially, under transaminase\u2010guided monitoring, low\u2010dose GFD\u2010CD3 effectively eliminated senescent cells and alleviated age\u2010related pathologies in aged mice and non\u2010human primates without adverse effects. These findings establish GFD\u2010CD3 as a clinically translatable senolytic agent and provide the compelling preclinical evidence for BiTE as a senolytic strategy.<\/jats:p>","DOI":"10.1111\/acel.70742","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:54:24Z","timestamp":1790657664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>uPAR<\/scp>\n                    \u2010Targeting T Cell Engager Exerts Senolytic Effects in Mice and Non\u2010Human Primates With Serum Aminotransferase Activity as a Safety Monitor"],"prefix":"10.1111","volume":"25","author":[{"given":"Jian","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-3041","authenticated-orcid":false,"given":"Xiaozhu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory 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Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanzhen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Kunming Institute of Zoology &amp; National Resource Center for Non\u2010Human Primates Chinese Academy of Sciences  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease\u2010Related Molecular Network West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-1835","authenticated-orcid":false,"given":"Ben","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Targeting Therapy &amp; Immunology and Laboratory of Cell Engineering &amp; Immunotherapy, Cancer Center 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