Definition

An engineered, human immunoglobulin (Ig) G1 monoclonal antibody directed against the negative immune checkpoint regulatory protein V-domain Ig suppressor of T-cell activation (VISTA; programmed death 1 homolog; PD1H; PD-1H), with potential negative immune checkpoint regulatory and antineoplastic activities. Upon administration, anti-VISTA monoclonal antibody KVA12123 targets and binds to VISTA on myeloid cells and T cells within the tumor microenvironment (TME). This inhibits VISTA-mediated signaling, decreases the presence of monocytic myeloid-derived suppressor cells (MDSCs), increases the presence of natural killer cells (NKs), activates dendritic cells (DCs) and abrogates VISTA-induced suppression of T-lymphocyte immune responses. This enhances cytotoxic T-cell infiltration, proliferation and activation within the TME, increases cytokine production by T cells, and inhibits tumor cell growth. VISTA, a negative checkpoint molecule of immune activation, is highly expressed on myeloid cells, T cells and in several tumor types. It plays a key role in the suppression of T-cell function.