[Combined gene therapy for murine liver cancer with interleukin-18 and cytosine deaminase genes].
OBJECTIVE
To investigate the synergistic antitumor effects of murine IL-18 and CD/5FC gene therapy on mice bearing liver cancer.


METHODS
A retrovirus vector pGCEN/IL-18 containing murine interleukin-18 gene was constructed. The retrovirus carrying IL-18 gene was used to infect murine liver cancer cell MM45T.Li, and proved to secret biological active IL-18. In mice bearing liver cancer, (60)Co-irradiated MM45T.Li/IL-18 vaccine was inoculated subcutaneously once a week for two weeks, and/or AdCD was injected intratumorally with 5FC injected i.p. for 8 days.


RESULTS
Thirty days from the treatment, the tumor volume of control group was 1580 approximately 1625 mm(3), MM45T.Li/IL-18 vaccine group was 366 +/- 159 mm(3), AdCD/5FC group was 438 +/- 65 mm(3), and combined IL-18 and AdCD/ 5FC therapy group was 15 +/- 7 mm(3) (P<0.05). The tumor volume in single gene therapy group reduced to the smallest after three-week treatment, but grew large again, while the tumor volume in combined therapy group still remained small. The median survival time in control group was 50.0 approximately 51.5 days, MM45T.Li/IL-18 group was 65 days, AdCD/5FC group was 57 days versus 75 days for combined gene therapy group (P<0.05), and with more abundant infiltration of CD4+ and CD8+ lymphocytes around the tumor in combined gene therapy group.


CONCLUSIONS
Combined gene therapy with IL-18 and CD/5FC can reduce the tumor volume and elicit the antitumor immunity of the host, which is superior to the single gene therapy for murine liver cancer.
Sun
W
W
Research Center for Human Gene Therapy, Department of Biochemistry & Molecular Biology, Shanghai Second Medical University, Shanghai 200025, China.
Tang
Z
Z
Wei
D
D
Tang
Y
Y
Chen
S
S
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase; D004195:Disease Models, Animal; D005437:Flucytosine / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000235:genetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics / Q000627:therapeutic use*; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D020382:Interleukin-18; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase