Preferred Label : Oncolytic HSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386;
NCIt synonyms : Oncolytic Virus STI-1386; oHSV-1-expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386; Oncolytic HSV-1 STI-1386; oHSV-1 Expressing Anti-PD-1 scFv-Fc/TGFbRII Decoy/IL-12 STI-1386;
NCIt definition : 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.;
Drug name : Seprehvec;
Molecule name : STI-1386; STI 1386;
NCI Metathesaurus CUI : CL1792416;
Origin ID : C187651;
UMLS CUI : C5706420;
Semantic type(s)
- concept_is_in_subset
