Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect.
Oncolytic viruses have shown considerable promise in the treatment of solid tumors, but their potency must be improved if their full clinical potential is to be realized. We inserted the gene encoding a truncated form of the gibbon ape leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. Furthermore, by controlling GALV.fus expression through a strict late viral promoter, whose activity depends on the initiation of viral DNA replication, we were able to express this glycoprotein in tumor cells but not in normal nondividing cells. It will be of interest to confirm whether functional expression of a strong fusogenic gene by an oncolytic herpes simplex virus enhances viral antitumor activity without increasing its toxicity.
Fu
Xinping
X
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Tao
Lihua
L
Jin
Aiwu
A
Vile
Richard
R
Brenner
Malcolm K
MK
Zhang
Xiaoliu
X
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology; D002455:Cell Division; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000008:administration & dosage; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy / Q000821:virology; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy / Q000821:virology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology; D018139:Simplexvirus / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D004279:DNA, Viral; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D049452:Green Fluorescent Proteins