Definition

A human immunoglobulin G1 (IgG1) monoclonal antibody directed against poliovirus receptor-related immunoglobulin (PVRIG; PVR Related Immunoglobulin Domain Containing Protein; CD112R), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PVRIG monoclonal antibody GSK4381562 targets and binds to PVRIG expressed on cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells within the tumor microenvironment (TME), thereby blocking the interaction of PVRIG with its ligand nectin cell adhesion molecule 2 (poliovirus receptor-related 2; PVRL2; CD112), which is overexpressed on a variety of tumor cell types. This abrogates the PVRIG-mediated inhibition of T-lymphocyte and NK-cell activation. This activates CTLs and NK cells, enhances anti-tumor responses and immune-mediated tumor cell killing, and inhibits tumor cell proliferation. PVRIG, a member of the B7/CD28 family and an immune checkpoint receptor, negatively regulates the activation of various immune cells upon activation and plays a key role in immunosuppression.