Definition

A recombinant humanized immunoglobulin G4 (IgG4) monoclonal antibody 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 JS009 targets and binds to PVRIG expressed on cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells within the tumor microenvironment (TME). This blocks 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. Inhibiting the activation of PVRIG abrogates the PVRIG-induced 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 that, upon activation, negatively regulates the activation of various immune cells. It plays a key role in immunosuppression.