PVRIG (CD112R)

Class

Anti-PVRIG monoclonal antibody (immune checkpoint inhibitor)

Pathway

DNAM-1/TIGIT/PVRIG axis of NK- and T-cell inhibition

PVRIG, also known as CD112R, is an inhibitory receptor expressed on natural killer (NK) cells and subsets of T cells. It belongs to a family of related receptors—alongside DNAM-1 and TIGIT—that read out signals from a shared set of ligands on other cells, most notably nectin and nectin-like proteins found on many tissues and frequently overexpressed on tumor cells. When PVRIG engages its ligand, nectin-2 (also called CD112), it dampens the activating signal that would otherwise be delivered through DNAM-1, effectively restraining cytotoxic activity. Blocking PVRIG with a monoclonal antibody is intended to remove this brake, allowing DNAM-1 to signal more freely and restoring the capacity of NK and T cells to recognize and kill tumor cells that display nectin-2. Because PVRIG operates through a ligand distinct from the one recognized by TIGIT, this approach is often considered complementary to TIGIT blockade or to broader checkpoint inhibition strategies, targeting a parallel arm of the same inhibitory network rather than duplicating it. This mechanism is broadly relevant across solid tumors where nectin-2 expression is common and where existing checkpoint therapies leave residual, unaddressed inhibitory signaling.