[Antitumor effect of combined therapy with adenovirus-mediated CD suicide gene and interleukin 2 gene transfer and its immunological mechanism].
OBJECTIVE
Adenovirus harboring E. coli cytosine deaminase gene(AdCD) and adenovirus harboring interleukin 2 gene (AdIL-2) were used for the combined treatment of established tumors in vivo.


METHODS
C57BL/6 mice were inoculated with B16F10 melanoma cells and 3 days later received at the tumor site injections of AdCD and/or AdIL-2 followed by i.p. injection of 5-fluorocytosine (5-Fc) 300 mg/kg per day for 10 days.


RESULTS
Mice received combined therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5-Fc, AdIL-2, control adenovirus AdlacZ/5-FC, or PBS. To investigate the immunological mechanism of the antitumor effects of the combined treatment it was found to induce enhanced natural killer cell activity and specific cytotoxic T cell activity. FACS analysis demonstrated that AdIL-2/AdCD/5-Fc therapy increased the expression of H-2Kb and B7-1 on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly.


CONCLUSIONS
Transfer of CD suicide gene plus 5-Fc combined with transfer of IL-2 gene synergistically inhibits the growth of melanoma in mice. Besides the cytotoxic effect of 5-Fc, specific and non-specific antitumor immunity might be responsible for the therapeutic effect. The combined therapy might have therapeutic potentials for human cancer.
Department of Immunology, Second Military Medical University, Shanghai.
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Ju
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Cao
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Wang
D000256:Adenoviridae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005798:Genes, Bacterial; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics*; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase