Construction and characterization of an oncolytic HSV vector containing a fusogenic glycoprotein and prodrug activation for enhanced local tumor control.
A large number of oncolytic viral vectors are currently under clinical development for cancer therapy. Herpes simplex virus type 1 (HSV-1) has demonstrated particular promise in this field, showing genetically engineered selective tumor replication and cytotoxicity in a wide variety of tumor types, without damaging healthy tissues. Enhanced activity has been observed when a range of therapeutic genes has been inserted into various oncolytic HSV genomes. Here, we discuss methods used to develop and characterize an oncolytic HSV virus that combines expression of a highly potent prodrug activating gene (yeast cytosine deaminase/uracil phosphoribosyltransferase fusion [Fcy::Fur]) and the fusogenic glycoprotein from gibbon ape leukemia virus (GALV) for enhanced local tumor control.
Simpson
Guy R
GR
Department of Oncology, Postgraduate Medical School, University of Surrey, Manor Park, UK.
Coffin
Robert S
RS
D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005822:Genetic Vectors / Q000235:genetics*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D050504:Oncolytic Viruses / Q000235:genetics*; D010957:Plasmids; D011355:Prodrugs / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae; D018139:Simplexvirus / Q000235:genetics*
D006023:Glycoproteins; D011355:Prodrugs; D011993:Recombinant Fusion Proteins