In vivo antitumor effect of herpes simplex virus thymidine kinase gene therapy in rat hepatocellular carcinoma: feasibility of adenovirus-mediated intra-arterial gene delivery.
Transfer of the herpes simplex virus-thymidine kinase gene, followed by the administration of ganciclovir (HSV-tk/GCV), has been a major approach for cancer gene therapy. We investigated the antitumor effect of the HSV-tk/GCV strategy with the rat orthotopic hepatocellular carcinoma (HCC) model and the tumor-selective gene delivery by an adenovirus-mediated gene transfer through the hepatic artery. The complete antitumor effect was demonstrated, after the treatment with GCV in rat HCC established by the implantation of HSV-tk transferred rat HCC cells. The in vivo bystander effect was also observed. The marked infiltration of CD4+ and CD8+ T lymphocytes, macrophages and NK cells were found in the tumor area. After the injection of adenovirus carrying the LacZ gene into the hepatic artery, the selective expression of transgene in the tumor cell was achieved. These findings indicate that the HSV-tk/GCV strategy, using an adenoviral vector, could be a promising avenue for the treatment of hepatocellular carcinoma.
Kwon
H C
HC
Laboratory of Molecular Oncology, Korea Cancer Center Hospital, Seoul. cmkim53@orgio.net
Kim
J H
JH
Kim
K C
KC
Lee
K H
KH
Lee
J H
JH
Lee
B H
BH
Lee
K H
KH
Jang
J J
JJ
Lee
C T
CT
Lee
H
H
Kim
C M
CM
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051381:Rats; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir