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.
Key WordsCancer therapy fusogenic membrane glycoproteins (FMG) herpes simplex virus type 1 (HSV-1) oncolytic, prodrug activation therapy
We thank Dr. Georgina Platt and Marianna Anesti for advice and proofreading of the chapter.
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