Evidence map›Paper›PMID 42806572›Full record

ArticleAging cell2026

uPAR-Targeting T Cell Engager Exerts Senolytic Effects in Mice and Non-Human Primates With Serum Aminotransferase Activity as a Safety Monitor.

Jian Deng, Xiaozhu Zeng, Jing Guo, Lihong Li, Shirui Zou, Nan Liu, Shuai He, Lanzhen Yan, Qiong Wang, Yongjie Zhu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jian DengDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xiaozhu ZengDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0002-2531-3041
Jing GuoDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lihong LiKunming Institute of Zoology & National Resource Center for Non-Human Primates, Chinese Academy of Sciences, Kunming, Yunnan, China.
Shirui ZouDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Nan LiuDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Shuai HeDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lanzhen YanDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Qiong WangKunming Institute of Zoology & National Resource Center for Non-Human Primates, Chinese Academy of Sciences, Kunming, Yunnan, China.
Yongjie ZhuDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Ben WangCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-4134-1835
Dong YangDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Longbao LvKunming Institute of Zoology & National Resource Center for Non-Human Primates, Chinese Academy of Sciences, Kunming, Yunnan, China.
Xudong ZhaoDepartment of Targeting Therapy & Immunology and Laboratory of Cell Engineering & 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-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0001-9126-7365

Funding

Sichuan Province Science and Technology Support Program 2025NSFJQ0057Sichuan Province Science and Technology Support Program 2026NSFSC0124Yunnan Science and Technology Talent and Platform Program 202405AD350052
6 · The paper itself

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.

Indexed as

SenotherapeuticsT-LymphocytesAnimalsCellular SenescenceHumansMiceSenotherapeuticssenescent cellsenolyticsT cell engageruPAR

Identifiers

PMID42806572
PMCPMC13620297

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.