anti-TIGIT/anti-PVRIG bispecific antibody SIM0348

{
  "id": "MLC-T-ONC-011129",
  "term": "anti-TIGIT/anti-PVRIG bispecific antibody SIM0348",
  "field": "Oncology and biomedicine",
  "definition": "A humanized immunoglobulin G1 (IgG1)-based bispecific antibody directed against both the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) and poliovirus receptor-related immunoglobulin (PVRIG; PVR Related Immunoglobulin Domain Containing Protein; CD112R), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-TIGIT/anti-PVRIG bispecific antibody SIM0348 simultaneously targets, binds to and inhibits TIGIT and PVRIG and their downstream signaling pathways. Inhibition of TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs), prevents the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8+ T cells. This leads to CD226 dimerization and CD226-mediated signaling and activates the immune system to exert a T-cell-mediated immune response against cancer cells. Inhibition of PVRIG expressed on cytotoxic T lymphocytes (CTLs) and NK cells within the tumor microenvironment (TME) blocks the interaction of PVRIG with its ligand CD112, which is overexpressed on a variety of tumor cell types. This abrogates the PVRIG-mediated inhibition of T-lymphocyte and NK cell activation. This activates CTLs and NK cells, enhances anti-tumor responses and immune-mediated tumor cell killing, and inhibits tumor cell proliferation. In addition, SIM0348 induces Fc-mediated killing of TIGIT-expressing immunosuppressive regulatory T cells (Tregs) and Tregs expressing TIGIT and PVRIG. TIGIT, a member of the immunoglobulin super family (IgSF) and an immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses. PVRIG, a member of the B7/CD28 family and an immune checkpoint receptor, negatively regulates the activation of various immune cells upon activation and plays a key role in immunosuppression.",
  "synonyms": [
    "anti-PVRIG/anti-TIGIT bispecific antibody SIM0348",
    "anti-TIGIT/PVRIG bispecific antibody SIM0348",
    "TIGIT x PVRIG bispecific antibody SIM0348"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/anti-tigit-anti-pvrig-bispecific-antibody-sim0348/"
}