{"id":"doi:10.1111/acel.70742","kind":"article","title":"uPAR-Targeting T Cell Engager Exerts Senolytic Effects in Mice and Non-Human Primates With Serum Aminotransferase Activity as a Safety Monitor","authors":["Deng J","Zeng X","Guo J","Li L","Zou S","Liu N","He S","Yan L","Wang Q","Zhu Y","Wang B","Yang D","Lv L","Zhao X"],"author_count":14,"year":2026,"published":"2026-10-01","venue":"Aging cell","cited_by":0,"doi":"10.1111/acel.70742","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.70742","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.70742","updated":null,"pmid":"42806572","pmcid":"PMC13620297","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13620297/pdf","abstract":"Senolytic CAR-T cells targeting uPAR induce dose-dependent toxicities. Although dosage adjustment mitigates these toxicities in laboratory mice, clinical translation remains challenging owing to the unpredictability of CAR-T cell proliferation across heterogeneous patient populations. In contrast, bispecific T-cell engagers (BiTEs) offer a safer alternative with superior dose-titratability. Here, we have developed a GFD-CD3 BiTE by employing the growth factor-like domain (GFD) of the natural ligand uPA as the targeting moiety to target uPAR-positive senescent cells. Dose-range finding studies revealed that high-dose GFD-CD3 predominantly induced hepatotoxicity through T cell-mediated attack on hepatic endothelial cells. Crucially, under transaminase-guided monitoring, low-dose GFD-CD3 effectively eliminated senescent cells and alleviated age-related pathologies in aged mice and non-human primates without adverse effects. These findings establish GFD-CD3 as a clinically translatable senolytic agent and provide the compelling preclinical evidence for BiTE as a senolytic strategy.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"uPAR-Targeting T Cell Engager Exerts Senolytic Effects in Mice and Non-Human Primates With Serum Aminotransferase Activity as a Safety Monitor\" by Deng J, Zeng X, Guo J et al., https://doi.org/10.1111/acel.70742, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}