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, 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.