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

Article · 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

- Archive id: doi:10.1111/acel.70742
- Published: 2026-10-01
- Venue: Aging cell
- DOI: https://doi.org/10.1111/acel.70742
- PMID: 42806572
- PMCID: PMC13620297
- Citations: 0
- Source URL: https://doi.org/10.1111/acel.70742
- PDF: https://europepmc.org/articles/PMC13620297/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

Cited in dossiers:
- [Biology of Aging & Longevity: State of the Field (October 2026)](https://space-kitty.com/dossiers/aging-longevity)

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