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- NCIT_C198990 IAO_0000115 "A bifunctional fusion protein composed of a humanized Fc-mutant anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody fused to transforming growth factor beta (TGF-beta) receptor type II (TGFbetaRII), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration of anti-TIGIT antibody/TGFbeta-RII fusion protein AK130, the TGFbetaRII moiety targets, binds to and neutralizes TGF-beta while the anti-TIGIT antibody moiety simultaneously targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs) and natural killer (NK) cells. The neutralization of TGF-beta prevents TGF-beta-mediated immunosuppressive signaling, thereby enhancing anti-tumor immunity in the tumor microenvironment (TME). The binding to TIGIT 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), and enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1) expressed on immune cells, such as 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. TIGIT, a member of the Ig superfamily (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. TGF-beta, dysregulated in many types of cancer, plays a key role in immunosuppression in the TME and is involved in tumor cell proliferation and tumor progression. The mutations in the Fc region of the anti-TIGIT antibody moiety prevent antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and the resulting loss of lymphocytes." @default.
- NCIT_C198990 NCIT_A7 NCIT_C126125 @default.
- NCIT_C198990 NCIT_A7 NCIT_C20457 @default.
- NCIT_C198990 NCIT_A7 NCIT_C20458 @default.
- NCIT_C198990 NCIT_A7 NCIT_C20459 @default.
- NCIT_C198990 NCIT_NHC0 "C198990" @default.
- NCIT_C198990 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C198990 NCIT_P108 "Anti-TIGIT Antibody/TGFbeta-RII Fusion Protein AK130" @default.
- NCIT_C198990 NCIT_P322 "GDC" @default.
- NCIT_C198990 NCIT_P399 "812198" @default.
- NCIT_C198990 normalizedInformationContent "100" @default.
- NCIT_C198990 referenceCount "1" @default.
- NCIT_C198990 hasExactSynonym "AK 130" @default.
- NCIT_C198990 hasExactSynonym "AK-130" @default.
- NCIT_C198990 hasExactSynonym "AK130" @default.
- NCIT_C198990 hasExactSynonym "Anti-TIGIT Antibody/TGFbeta-RII Fusion Protein AK130" @default.
- NCIT_C198990 hasExactSynonym "TIGIT/TGF-beta Dual-targeting Antibody Fusion Protein AK130" @default.
- NCIT_C198990 inSubset NCIT_C128784 @default.
- NCIT_C198990 inSubset NCIT_C157711 @default.
- NCIT_C198990 inSubset NCIT_C157712 @default.
- NCIT_C198990 inSubset NCIT_C176424 @default.
- NCIT_C198990 type Class @default.
- NCIT_C198990 isDefinedBy ncit.owl @default.
- NCIT_C198990 label "Anti-TIGIT Antibody/TGFbeta-RII Fusion Protein AK130" @default.
- NCIT_C198990 subClassOf NCIT_C129820 @default.
- NCIT_C198990 subClassOf NCIT_C1908 @default.
- NCIT_C198990 subClassOf NCIT_C1909 @default.
- NCIT_C198990 subClassOf NCIT_C198990 @default.
- NCIT_C198990 subClassOf NCIT_C274 @default.
- NCIT_C198990 subClassOf NCIT_C308 @default.