Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.
Gene therapy using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of the 0.3-kb human alpha-fetoprotein (AFP) gene promoter (LNAF0.3TK virus) in combination with ganciclovir (GCV) treatment was performed in athymic mice harboring AFP-producing HuH-7 human hepatoma cells. GCV treatment resulted in pronounced growth inhibition of the virus-infected HuH-7 xenograft in mice, but did not affect growth of the parental xenograft. These results indicate that the AFP gene promoter sequence allows enough therapeutic gene expression to induce the GCV-mediated cytotoxicity in vivo in AFP-producing human hepatoma cells.
Ueki
T
T
The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852, Japan.
Nakata
K
K
Mawatari
F
F
Tsuruta
S
S
Ido
A
A
Ishikawa
H
H
Nakao
K
K
Kato
Y
Y
Ishii
N
N
Eguchi
K
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy* / Q000821:virology; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics
D000509:alpha-Fetoproteins; D013937:Thymidine Kinase; D015774:Ganciclovir