[Recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene transfer followed by ganiciclovir administration effectively inhibits growth of human small-cell lung cancer in a murine xenotransplant model].
OBJECTIVE
Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer in combination with ganiciclovir (GCV) is one of the major gene therapy strategies to eradicate tumor cells. This study was aimed at determining the in vivo anti-tumor efficacy of ADV-TK in combination with ganiciclovir (GCV).


METHODS
A murine xenotransplant model of human small-cell lung cancer was established. ADV-TK was administrated by intra-tumoral injection followed by intraperitoneal administration of GCV. The anti-tumor efficacy was evaluated using index of tumor volume, relative tumor volume, tumor weight, relative tumor proliferative rate, and tumor growth curve.


RESULTS
In the presence of GCV, ADV-TK effectively inhibited growth of human small-cell lung cancer in a dose-dependent fashion. An inhibition plateau was not observed within the current dosage range. ADV-TK at a dose of 6.0 x 10(9) viral particles/kg in the presence of GCV lead to 64.6% and 81.7% inhibition of tumor growth respectively in two independent experiments. ADV-TK or GCV alone caused slight inhibition of tumor growth, which was not statistically significant as compared to the negative control group (P > 0.05).


CONCLUSIONS
ADV-TK followed by GCV is highly efficacious to inhibit the growth of human small-cell lung cancer in a murine xenotransplant model. The results presented here are encouraging to warrant a further clinical evaluation of the potential therapeutic benefits of this strategy.
Zhou
Jian-feng
JF
Biomedical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Chen
Gang
G
Lu
Yun-ping
YP
Wang
Shi-xuan
SX
Ma
Ding
D
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018288:Carcinoma, Small Cell / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000235:genetics*; D014183:Transplantation, Heterologous
D013937:Thymidine Kinase; D015774:Ganciclovir