VISTA inhibitors in cancer immunotherapy: a short perspective on recent progresses

Abstract

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is a novel negative checkpoint regulator that mediates T cell proliferation and cytokine production. The VISTA signaling pathway blockade has been proved as a promising strategy for cancer immunotherapy. Recent VISTA sequence analysis and crystal structure investigations have revealed its independent and unique function as compared with B7 family members, such as PD-1. This review will discuss VISTA binding partners and compare the structural differences between VISTA and other B7 family members, focusing on VISTA functions in immune activation and maintaining T cell quiescence. Recent progress and the therapeutic potential of biomacromolecules, such as monoclonal antibodies (mAbs) and small molecules targeting VISTA, are also discussed. Among these, a first-in-class small-molecule antagonist, CA-170, is highlighted.