Poliovirus receptor-related 2 (Nectin-2) (PVRL2)

Poliovirus receptor-related 2 (PVRL2), also known as Nectin-2 or CD112, is a transmembrane glycoprotein belonging to the Nectin family and the immunoglobulin superfamily. It is a key component of adherens junctions, where it mediates cell-cell adhesion through homophilic and heterophilic interactions. In addition to its structural role, PVRL2 serves as a critical immune checkpoint ligand that is frequently overexpressed in various cancers, including ovarian, endometrial, and lung carcinomas. It modulates immune cell activity by binding to several receptors on T cells and natural killer (NK) cells: the inhibitory receptors PVRIG (CD112R) and TIGIT, and the activating receptor DNAM-1 (CD226). The interaction between PVRL2 and PVRIG is a potent immunosuppressive pathway that tumors exploit to evade immune surveillance. Consequently, PVRL2 is a significant therapeutic target in oncology, with drug development efforts focusing on blocking its interaction with inhibitory receptors. While direct anti-PVRL2 antibodies are primarily in preclinical stages, agents like COM701 (an anti-PVRIG antibody) are being evaluated in clinical trials to disrupt this axis and enhance anti-tumor immunity.

Other names

Nectin-2CD112PRR2HVEBPoliovirus receptor-related protein 2Herpesvirus entry mediator B

Immune checkpoint inhibition by blocking the interaction between PVRL2 and its inhibitory receptors PVRIG or TIGIT to restore T cell and NK cell anti-tumor activity.