Preferred Label : Oncolytic HSV-1 rRp450;
NCIt definition : A gene therapy agent containing an attenuated, replication-competent, genetically
engineered mutant form of the Herpes simplex virus 1 (HSV-1) strain KOS with potential
antineoplastic activity. Upon infusion into the hepatic artery, oncolytic HSV-1 rRp450
replicates in hepatocellular carcinoma (HCC) cells and exerts direct cytotoxic effects
eventually disrupting cancer cell membranes and liberating progeny virions thereby
infecting adjacent tumor cells. In addition, rRp450 expresses the cytochrome P450
transgene that activates oxazaphosphorines, such as cyclophosphamide (CPA). Therefore,
CPA can become activated in the presence of rRp450 and exert its antineoplastic effect.
rRp450 is deleted for the HSV-1 gene UL39, encoding the viral ribonucleotide reductase
large subunit infected cell protein 6 (ICP6), thereby disrupting the activity of viral
ribonucleotide reductase and resulting in the inhibition of nucleotide metabolism
and viral DNA synthesis in nondividing cells but not in dividing cells. UL39 is replaced
by the rat CYP2B1 gene, encoding a cytochrome P450 enzyme that activates oxazaphosphorines.
rRp450 also expresses viral thymidine kinase, which activates the cancer prodrug ganciclovir.;
Molecule name : rRp450;
NCI Metathesaurus CUI : CL416247;
Origin ID : C90563;
UMLS CUI : C2983763;
Semantic type(s)
- concept_is_in_subset
