Poliovirus receptor-related protein 2 (CD112) (PVRL2)

Poliovirus receptor-related protein 2 (PVRL2), also known as CD112 or Nectin-2, is a cell-surface glycoprotein belonging to the nectin family of the immunoglobulin superfamily. It plays a fundamental role in organizing adherens junctions through interactions with other nectins and the intracellular protein afadin. In oncology and immunology, PVRL2 is recognized as a critical immune checkpoint ligand that modulates the activity of T-cells and natural killer (NK) cells by binding to the inhibitory receptors PVRIG (CD112R) and TIGIT, as well as the costimulatory receptor DNAM-1 (CD226). PVRL2 is frequently overexpressed in a wide range of solid tumors and hematological malignancies, where it facilitates immune evasion by suppressing lymphocyte-mediated anti-tumor responses. Therapeutic strategies targeting the PVRL2 axis primarily involve monoclonal antibodies, such as COM701, which block its interaction with PVRIG to restore immune surveillance. While direct anti-PVRL2 antibodies are being investigated in preclinical settings, clinical development has largely focused on modulating its receptors to enhance the efficacy of cancer immunotherapies.

Other names

Nectin-2CD112Herpesvirus entry mediator BHVEBPRR2

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