Intratumoral injection of GM-CSF gene encoded recombinant vaccinia virus elicits potent antitumor response in a mixture melanoma model

Cancer Gene Ther. 1997 Mar-Apr;4(2):139-44.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / genetics
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Histocompatibility Antigens Class I / drug effects
  • Histocompatibility Antigens Class I / metabolism
  • Injections, Intralesional
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Melanoma / genetics
  • Melanoma / pathology*
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Phagocytosis / drug effects
  • Phagocytosis / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Survival Rate
  • Tumor Cells, Cultured
  • Vaccinia / genetics*


  • Histocompatibility Antigens Class I
  • Recombinant Proteins
  • Nitric Oxide
  • Granulocyte-Macrophage Colony-Stimulating Factor