TIGIT is a co-inhibitory receptor that is highly expressed in Natural Killer (NK) cells, activated CD4+, CD8+ and regulatory T cells. Interaction with the poliovirus receptor (PVR; CD155) on antigen presenting cells, such as dendritic cells, recruits Src homology (SH) domain-containing protein tyrosine phosphatase SHP1 and SHP2 or the inositol phosphatase SHIP1 and SHIP2 to the TIGIT ITIM domain. This increases IL-10 release and suppresses NF-kB and NFAT T cell receptor (TCR) signaling, which blocks T cell proliferation and cytokine production. It serves as a competitive inhibitor of CD226, a co-stimulatory receptor for CD155. TIGIT targeting antibodies that block this T cell-intrinsic inhibitory effects have shown enhanced anti-tumor and anti-viral functions in preclinical studies.

PVRIG (CD112R) is an regulatory protein expressed on T-cells which inhibits immune activation when binding to its counterpart on APCs, PVRL2 (CD112, Nectin-2). Since both PVRL2 and PVR can activate DNAM-1 (CD226), PVRIG works synergistically with and separately from TIGIT. PVRL2 is overexpressed in a variety of tumor types, including breast and ovarian cancers, suggesting that its interaction with PVRIG is a major mechanism of immune suppression in those diseases.

Figure 1. Recombinant TIGIT/PVRIG Dual Effector Reporter Cell constitutively expressing TIGIT.

Figure 2. Recombinant TIGIT/PVRIG Dual Effector Reporter Cell constitutively expressing PVRIG.

Figure 3. Dose Response of Blocking Antibodies in TIGIT/PVRIG Dual Effector Reporter Cells(C45) With CD112/CD155 Dual aAPC Cells.