Novel PD-L1/VISTA Dual Inhibitor as Potential Immunotherapy Agents.

Inhibiting the activity of immune checkpoint proteins to reignite the antitumor activity of immune cells has emerged as a pivotal strategy. PD-L1 and VISTA, as critical proteins governing immune regulation, are concurrently upregulated under conditions such as hypoxia. Through a rational drug design process, , a dual-target inhibitor for PD-L1 and VISTA is identified. This inhibitor blocks the signaling pathways of both PD-L1 and VISTA at the protein and cellular levels, thereby reactivating the antitumor function of T cells. displays encouraging attributes in terms of druggability and safety assessments. Notably, demonstrates superior antitumor efficacy compared to single-target inhibitors at equivalent doses in in vivo experiments. More crucially, significantly enhances the infiltration of immune cells. This study not only validates the effectiveness of a dual-target inhibitor strategy against PD-L1 and VISTA, but also identifies as a promising candidate molecule with significant therapeutic potential.