Study on the killing effect of natural killer cells combined with ATF-Fc recombinant protein on uPAR high-expressing cell lines

Abstract Aging and cancer are interconnected, with studies suggesting that the aging-related secretory phenotype can induce transformation between epithelial and stromal cells, as well as tumor angiogenesis. This connection suggests the feasibility of a treatment strategy that simultaneously targets tumor cells and aging cells. Urine plasminogen activator receptor (uPAR) is highly expressed in both tumor and aging cells but lowly expressed in normal cells, making it a common target for anti-aging and anti-cancer therapies. This study aims to discuss an engineered antibody that, when combined with NK cells, exerts antibody-dependent cytotoxicity to clear cells with high uPAR expression. An ATF-Fc fusion protein, constructed by linking the uPAR ligand urokinase plasminogen activator (upa) binding domain (ATF) to the human IgG1 Fc fragment, was used to evaluate the killing effect of the combined antibody and NK cells on cells with high uPAR expression. In vitro experiments showed that ATF-Fc could specifically bind to cells overexpressing uPAR and promote their apoptosis. Animal experiments also confirmed the killing effect of ATF-Fc, which was enhanced when combined with NK cells. ATF-Fc antibody inhibited the proliferation of cells with high uPAR expression, with the synergistic killing effect of this antibody combined with NK cells being particularly significant.