Intratumoral injection of GM-CSF gene encoded recombinant vaccinia virus elicits potent antitumor response in a mixture melanoma model.
A recombinant vaccinia virus containing and expressing the gene for murine granulocyte-macrophage colony-stimulating factor (VVGM-CSF) was constructed and tested for its antitumor activity. A murine tumor model was established by injecting 10(5) B16F10 melanoma cells into the right rear leg of C57BL/6 mice. Three days after B16F10 inoculation, VVGM-CSF or a thymidine kinase gene-deficient vaccinia virus (VVTK) were injected intratumorly twice weekly for 3 weeks. The results showed that VVGM-CSF treatment significantly inhibited the growth of subcutaneous tumor and delayed the survival period of tumor-bearing mice. Splenic lymphokine-activated killer cell, natural killer cell, and cytotoxic T lymphocyte activities were not found to be altered after VVGM-CSF or VVTK therapy. Cytotoxic and phagocytic activity of peritoneal macrophages were found to be greatly elevated in mice treated with VVGM-CSF. Nitric oxide released from the macrophages was also increased. Considering these data, we may speculate that continuous secretion of GM-CSF and activation of macrophages may contribute to the antitumor effects of VVGM-CSF injected intratumorally.
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Department of Immunology, Second Military Medical University, Shanghai, Peoples Republic of China.
Cao
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Acres
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D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000378:metabolism; D015552:Injections, Intralesional; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014615:Vaccinia / Q000235:genetics*
D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor