T Cells Targeting uPAR Remove Aged Cells in Mice and Primates with Liver Enzyme Levels Used to Monitor Safety

Low-dose GFD-CD3 effectively eliminated senescent cells in aged mice and non-human primates without adverse effects.

• High-dose GFD-CD3 caused hepatotoxicity primarily through T cell attacks on liver endothelial cells.
• Dose-range finding studies indicated that dosage adjustments can mitigate toxicities in laboratory mice.
• GFD-CD3 targets uPAR-positive senescent cells using the growth factor-like domain of the natural ligand uPA.
• Bispecific T-cell engagers (BiTEs) may provide a safer alternative to traditional CAR-T therapies due to superior dose-titratability.
• The findings support the potential of GFD-CD3 as a clinically translatable senolytic agent.

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