Nectin-1 and Nectin-2 (Nectin-1/2)

Nectin-1 (CD111) and Nectin-2 (CD112) are cell surface glycoproteins belonging to the immunoglobulin superfamily that function as calcium-independent cell-cell adhesion molecules (UniProt Q15223; UniProt Q92692). They are integral to the formation and maintenance of adherens junctions and tight junctions in various tissues. Beyond their structural roles, they serve as critical entry receptors for alphaherpesviruses, including Herpes Simplex Virus 1 and 2 (Geraghty et al., 1998, Science). In the context of immuno-oncology, Nectin-2 is a prominent ligand for the inhibitory receptors PVRIG (CD112R) and TIGIT, which are expressed on T cells and Natural Killer (NK) cells (Whelan et al., 2019, Cancer Immunology Research). By binding to these receptors, Nectin-2 contributes to an immunosuppressive tumor microenvironment, allowing cancer cells to evade immune surveillance. Consequently, therapeutic agents such as monoclonal antibodies (e.g., COM701, which targets the PVRIG receptor) are being developed to modulate these interactions and restore anti-tumor activity (ClinicalTrials.gov NCT03667716). Additionally, Nectin-1 is a primary target for oncolytic virus therapies like Talimogene laherparepvec, which utilize the receptor to selectively infect and lyse tumor cells (Liu et al., 2003, Gene Therapy). Targeting the Nectin-1/2 axis represents a promising strategy for both viral-based therapies and immune checkpoint blockade.

Other names

PVRL1CD111PRR1HIgRHVECPVRL2CD112PRR2HVEB

Modulation of the TIGIT/PVRIG/DNAM-1 signaling axis to enhance T-cell and NK-cell mediated anti-tumor immunity, and facilitation of viral entry for oncolytic therapy.