Preferred Label : Ad5-yCD/mutTKSR39rep-hIL12;
NCIt synonyms : Oncolytic Adenovirus Ad5-yCD/mutTKSR39rep-hIL12;
NCIt definition : A replication-competent oncolytic adenovirus encoding the murine pro-inflammatory
cytokine interleukin-12 (IL-12) gene and two suicide fusion genes, a yeast cytosine
deaminase (yCD) and a mutant form of herpes simplex virus type 1 thymidine kinase
(HSV-1 TKSR39), with potential immunomodulating and antineoplastic activities. Upon
intratumoral administration of Ad5-yCD/mutTKSR39rep-hIL12, the adenovirus selectively
infects and replicates in tumor cells, which results in direct tumor cell lysis. Synergistically,
IL-12 expressed by the adenovirus may activate the immune system by promoting the
activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g)
and inducing cytotoxic T-lymphocyte (CTL) responses against tumor cells, which may
result in immune-mediated tumor cell death, inhibition of tumor cell proliferation
and inhibition of tumor angiogenesis. In addition, Ad5-yCD/mutTKSR39rep-hIL12-infected
cancer cells express yCD and TKSR39; upon administration of the prodrugs 5-fluorocytosine
(5-FC) and valganciclovir (vGCV), the yCD and HSV-1 TKSR39 activate these prodrugs
to form 5-fluorouracil (5-FU) and ganciclovir, respectively. 5-FU gets converted to
5-fluoro-uridine monophosphate (5-FUMP) and subsequently to 5-fluoro-deoxyuridine
monophosphate (5-FdUMP); 5-FdUMP irreversible inhibits thymidylate synthase, inhibits
deoxythymidine triphosphate (dTTP) formation and halts DNA synthesis. Once phosphorylated
intracellularly, ganciclovir triphosphate competitively inhibits deoxyguanosine triphosphate
(dGTP) incorporation into DNA and inhibits DNA synthesis.;
NCI Metathesaurus CUI : CL498293;
Origin ID : C123930;
UMLS CUI : C4085935;
Semantic type(s)
- concept_is_in_subset
