Poliovirus receptor and Nectin-2 (PVR and PVRL2)

DNAM-1 ligands, primarily Poliovirus receptor (CD155) and Nectin-2 (CD112), are cell surface glycoproteins that serve as critical recognition molecules for the activating receptor DNAM-1 (CD226) expressed on γδ T cells and natural killer (NK) cells (PMID: 12649282). These ligands are frequently overexpressed in various malignancies, including melanoma, lung cancer, and colorectal cancer, as a result of cellular stress or oncogenic signaling (PMID: 14530338). When DNAM-1 binds to these ligands on tumor cells, it triggers γδ T cell activation, leading to the release of cytotoxic granules and pro-inflammatory cytokines like IFN-γ and TNF-α (PMID: 17202312). However, the therapeutic efficacy of this interaction is often limited by the presence of inhibitory receptors such as TIGIT and PVRIG, which bind the same ligands with higher affinity, thereby suppressing immune activity (PMID: 31435058). Current drug development strategies focus on blocking these inhibitory interactions using monoclonal antibodies to restore DNAM-1-mediated anti-tumor responses or targeting the ligands directly with engineered cell therapies (PMID: 32413319, PMID: 33806110).

Other names

CD155CD112DNAM-1 ligandsPoliovirus receptorNectin-2PVRL2Necl-5HveBCD226 ligands

Modulation of the DNAM-1/TIGIT/PVRIG axis to enhance γδ T cell-mediated tumor cell lysis by blocking inhibitory signals or promoting activating receptor engagement.