Adenovirus-mediated gene therapy of gastric carcinoma using cancer-specific gene expression in vivo.
The carcinoembryonic antigen (CEA) is a glycoprotein which overexpressed in the majority of human gastric cancers. We demonstrated that recombinant adenoviral vector (AdCEAtk), containing the CEA promoter, could transfer the herpes simplex virus thymidine kinase (HSVtk) gene into CEA-producing gastric cancer cells to confer sensitivity to ganciclovir (GCV) in vivo. In an ex vivo experiment, the tumor growth was inhibited after GCV treatment when the tumor contained more than 20% of AdCEAtk infected cells, indicating an efficient bystander killing effect. With intra-tumoral injection of AdCEAtk, the HSVtk were selectively expressed in approximately 30% of CEA producing cancer cells. By AdCEAtk injection and GCV administration, the growth of tumors was significantly inhibited by 20% as compared to untreated tumors. It is hoped that these results provide a strategy of tumor specific gene transfer for CEA producing gastric cancers.
Tanaka
T
T
Second Department of Internal Medicine, University of Tokyo, Japan.
Kanai
F
F
Lan
K H
KH
Ohashi
M
M
Shiratori
Y
Y
Yoshida
Y
Y
Hamada
H
H
Omata
M
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002277:Carcinoma / Q000628:therapy*; D015774:Ganciclovir / Q000008:administration & dosage; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000628:therapy*; D013937:Thymidine Kinase / Q000008:administration & dosage*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D002272:Carcinoembryonic Antigen; D013937:Thymidine Kinase; D015774:Ganciclovir