Definition

An immunoglobulin G4 (IgG4) 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 HMBD-002 targets and binds to VISTA on monocytes and T cells. This inhibits VISTA-mediated signaling, decreases the presence of monocytic myeloid-derived suppressor cells (MDSCs), increases the presence of activated dendritic cells (DCs) and abrogates VISTA-induced suppression of T-lymphocyte immune responses. This enhances cytotoxic T-cell infiltration, proliferation and activation within the tumor microenvironment (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.