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- NCIT_C187651 IAO_0000115 "A second-generation, genetically engineered oncolytic herpes simplex virus type 1 (oHSV-1) expressing a single-chain variable fragment (scFv)-Fc targeting the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279), a human transforming growth factor beta receptor 2 (TGFbRII) decoy and the human immunostimulating cytokine interleukin-12 (IL-12), with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic activities. Upon administration, oHSV-1 expressing anti-PD-1 scFv-Fc/TGFbRII decoy/IL-12 STI-1386 infects and replicates in tumor cells causing viral-mediated tumor cell lysis. The released virus particles, in turn, infect and replicate in neighboring tumor cells. Tumor antigens released from the lysed tumor cells also activate the immune system to induce a tumor-specific systemic immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected tumor cells. In addition, oHSV-1 expressing anti-PD-1 scFv-Fc/TGFbRII decoy/IL-12 STI-1386 promotes the secretion of anti-PD-1 scFv-Fc, TGFbRII decoy and IL-12 by the tumor cells. The anti-PD-1 scFv-Fc targets, binds to and inhibits PD-1 and its downstream signaling pathways. This may restore immune function through the activation of T-cells and T-cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T-cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death-1 ligand 1 (PD-L1) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity. The TGFbRII decoy targets and binds to TGF-beta and prevents the activation of TGF-beta-mediated signaling pathways in the tumor microenvironment (TME). This abrogates the TGF-beta-mediated immunosuppression in the TME. TGF-beta, a pro-inflammatory mediator, is upregulated in certain types of cancers and is involved in cancer cell proliferation, tumor progression, migration and invasion, and the suppression of the immune response. IL-12 promotes the activation of natural killer (NK) cells, which induces both the secretion of interferon-gamma and a CTL response against the tumor cells. This results in both immune-mediated tumor cell death and further inhibition of tumor cell proliferation." @default.
- NCIT_C187651 NCIT_NHC0 "C187651" @default.
- NCIT_C187651 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C187651 NCIT_P108 "Oncolytic HSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386" @default.
- NCIT_C187651 NCIT_P208 "CL1792416" @default.
- NCIT_C187651 NCIT_P322 "GDC" @default.
- NCIT_C187651 NCIT_P399 "809713" @default.
- NCIT_C187651 normalizedInformationContent "100" @default.
- NCIT_C187651 referenceCount "1" @default.
- NCIT_C187651 hasExactSynonym "Oncolytic HSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386" @default.
- NCIT_C187651 hasExactSynonym "Oncolytic HSV-1 STI-1386" @default.
- NCIT_C187651 hasExactSynonym "Oncolytic Virus STI-1386" @default.
- NCIT_C187651 hasExactSynonym "STI 1386" @default.
- NCIT_C187651 hasExactSynonym "STI-1386" @default.
- NCIT_C187651 hasExactSynonym "STI1386" @default.
- NCIT_C187651 hasExactSynonym "Seprehvec" @default.
- NCIT_C187651 hasExactSynonym "oHSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386" @default.
- NCIT_C187651 hasExactSynonym "oHSV-1-expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386" @default.
- NCIT_C187651 inSubset NCIT_C128784 @default.
- NCIT_C187651 inSubset NCIT_C157711 @default.
- NCIT_C187651 inSubset NCIT_C157712 @default.
- NCIT_C187651 inSubset NCIT_C176424 @default.
- NCIT_C187651 type Class @default.
- NCIT_C187651 isDefinedBy ncit.owl @default.
- NCIT_C187651 label "Oncolytic HSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386" @default.
- NCIT_C187651 subClassOf NCIT_C129821 @default.
- NCIT_C187651 subClassOf NCIT_C187651 @default.
- NCIT_C187651 subClassOf NCIT_C1908 @default.
- NCIT_C187651 subClassOf NCIT_C1909 @default.
- NCIT_C187651 subClassOf NCIT_C1962 @default.
- NCIT_C187651 subClassOf NCIT_C274 @default.
- NCIT_C187651 subClassOf NCIT_C307 @default.
- NCIT_C187651 subClassOf NCIT_C717 @default.