A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy.
The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xenografts. The potent bystander effect of the FMG transgene is a major contributor to the success of this approach but immunological activation may also be a factor. To our knowledge, this is the first demonstration in vivo of the potential both of FMG and lentiviral vectors for cancer gene therapy and highlights the importance of exploring different vector systems to complement the biological properties of the therapeutic transgene.
Diaz
R M
RM
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota, USA.
Bateman
A
A
Emiliusen
L
L
Fielding
A
A
Trono
D
D
Russell
S J
SJ
Vile
R G
RG
D000818:Animals; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D015552:Injections, Intralesional; D016086:Lentivirus / Q000235:genetics*; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000235:genetics*
D014760:Viral Fusion Proteins