Novel PD-L1/VISTA\nDual Inhibitor as Potential Immunotherapy\nAgents

Inhibiting the activity of immune checkpoint proteins\nto reignite\nthe antitumor activity of immune cells has emerged as a pivotal strategy.\nPD-L1 and VISTA, as critical proteins governing immune regulation,\nare concurrently upregulated under conditions such as hypoxia. Through\na rational drug design process, <b>P17</b>, a dual-target inhibitor\nfor PD-L1 and VISTA is identified. This inhibitor blocks the signaling\npathways of both PD-L1 and VISTA at the protein and cellular levels,\nthereby reactivating the antitumor function of T cells. <b>P17</b> displays encouraging attributes in terms of druggability and safety\nassessments. Notably, <b>P17</b> demonstrates superior antitumor\nefficacy compared to single-target inhibitors at equivalent doses\nin in vivo experiments. More crucially, <b>P17</b> significantly\nenhances the infiltration of immune cells. This study not only validates\nthe effectiveness of a dual-target inhibitor strategy against PD-L1\nand VISTA, but also identifies <b>P17</b> as a promising candidate\nmolecule with significant therapeutic potential.