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

This is the authors' abstract. We don't add key points for this paper.

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, P17, 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. P17 displays encouraging attributes in terms of druggability and safety assessments. Notably, P17 demonstrates superior antitumor efficacy compared to single-target inhibitors at equivalent doses in in vivo experiments. More crucially, P17 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 P17 as a promising candidate molecule with significant therapeutic potential.