Preferred Label : Oncolytic HSV-1 Expressing IL-12, IL-15/IL-15-receptor Alpha and PD-L1 Blocking Peptide
VG161;
NCIt synonyms : Recombinant IL12/15-IL-15Ra-PDL1B Oncolytic HSV-1; oHSV-1 Expressing IL-12, IL-15/IL-15Ra and PD-L1 Blocking Peptide VG161;
NCIt definition : A genetically engineered oncolytic herpes simplex virus type 1 (oHSV-1) expressing
the human immunostimulating cytokine interleukin (IL)-12, the immunostimulating cytokine
IL-15 and its receptor alpha unit (IL-15Ra), and a blocking peptide directed against
the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation
274; CD274), with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic
activities. The blocking peptide is a fusion protein composed of the TF peptide, derived
from fragments of human programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1)
protein, fused to an immunoglobulin G4 (IgG4) Fc (TF-Fc). Upon intratumoral administration,
oHSV-1 expressing IL-12, IL-15/IL-15Ra and PD-L1 blocking peptide VG161 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 IL-12, IL-15/IL-15Ra and
PD-L1 blocking peptide VG161 promotes the secretion of IL-12, IL-15/IL-15Ra and PD-L1
blocking peptide by the tumor cells locally in the TME. 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. IL-15 stimulates the proliferation of
NK cells, CTLs and memory T-cells, which induces an anti-tumor immune response. These
actions of the cytokines may increase tumor cell killing and decrease tumor cell proliferation.
PD-L1 blocking peptide targets, binds to and inhibits PD-L1, preventing the binding
and subsequent activation of its receptor, PD-1. This reverses T-cell inactivation
caused by PD-L1/PD-1 signaling, increases T-cell expansion and enhances the CTL-mediated
anti-tumor immune response. PD-L1, a transmembrane protein, is expressed on the surface
of antigen presenting cells (APCs) and on many cancer cell types. PD-L1 binding to
PD-1, a negative regulator of the immune system on activated T-cells, limits the expansion
and survival of CD8 T-cells, suppresses the immune system and results in immune evasion.
IL-15Ra complexed with IL-15 increases IL-15 signaling and IL-15 half-life upon expression.;
Molecule name : VG 161; VG-161;
NCI Metathesaurus CUI : CL1662396;
Origin ID : C179675;
UMLS CUI : C5555861;
Semantic type(s)
- Virus [UMLS semantic type]
- concept_is_in_subset
