Preferred Label : Oncolytic Herpes Simplex Virus-1 ONCR-177;
NCIt synonyms : Oncolytic HSV-1 ONCR-177; oHSV-1 ONCR-177;
NCIt related terms : ONCR-177;
NCIt definition : A recombinant, genetically modified, microRNA (miRNA)-attenuated oncolytic viral strain
of the herpes simplex type 1 (HSV-1) virus, with potential oncolytic, immunostimulating
and antineoplastic activities. In ONCR-177, a dual bidirectional promoter enables
the expression of five different transgenes: the natural killer (NK) cell and T-cell
activating cytokine interleuin-12 (IL-12), the chemokines C-C motif chemokine 4 (CCL4)
and the extracellular domain of the Fms-related tyrosine kinase 3 ligand (FLT3LG),
to allow for expansion and recruitment of classical dendritic cells (DCs), and antagonists
to the immune checkpoints programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated
antigen 4 (CTLA-4) to counter T cell exhaustion. Upon intra-tumoral administration,
the oncolytic HSV-1 ONCR-177 specifically targets, infects and selectively replicates
in tumor cells only while not infecting normal, healthy cells. This induces tumor
cell lysis. The released virus particles then infect and replicate in neighboring
tumor cells, thereby further killing tumor cells. The released tumor-associated antigens
(TAAs) from the tumor cells activate the immune system to exert an anti-tumor immune
response against the tumor cells, thereby further killing the tumor cells. In addition,
the expressed transgenes that are released upon tumor cell lysis induce a systemic
tumor-specific immune response and activate NKs, DCs and cytotoxic T-lymphocytes (CTLs)
while inhibiting regulatory T-cells (Tregs). This further kills nearby non-infected
tumor cells. In ONCR-177, the neurovirulence gene ICP34.5 allows for potent oncolysis,
even in the presence of host cell antiviral responses. To ensure selective replication
and oncolysis in cancer cells while attenuating replication in healthy tissue, tissue
specific miRNA-binding cassettes (miR-T) are inserted into early genes essential for
viral replication. In addition, UL37 mutation suppresses latent infection.;
UNII : 83P3OQ67ZT;
Molecule name : ONCR-177; ONCR 177;
NCI Metathesaurus CUI : CL1405762;
Origin ID : C171540;
UMLS CUI : C5417869;
Semantic type(s)
- Virus [UMLS semantic type]
- concept_is_in_subset
