Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF.
The efficacy of a recombinant vaccinia virus (rvv-mGM-CSF) expressing murine granulocyte-macrophage colony stimulating factor (GM-CSF) for use in cancer gene therapy was evaluated. C57BL/6 mice with established B16-F10 melanoma were treated by s.c. injection of irradiated B16 cells infected with two different recombinant vaccinia virus (rvv) constructs. Mice treated with rvv-mGM-CSF vaccine survived longer (p < 0.05), were free of palpable tumors (> 4 mm) longer (p < 0.02), and had smaller mean tumor volumes (p < 0.005) compared to those treated with irradiated B16 cells infected with a control rvv (rvv-lacZ) expressing Escherichia coli beta-galactosidase or irradiated uninfected B16 cells. The vaccine appeared to be B16 tumor cell specific, because there was no therapeutic effect when heterologous but syngeneic (H-2b) colon adenocarcinoma cells, MC-38 infected with rvv-mGM-CSF were used as vaccine. In this model, rvv expressing interleukin-2 (IL-2) was ineffective. In addition, experimental lung metastasis of B16 tumor cells was significantly inhibited by rvv-mGM-CSF vaccine compared to several control vaccines when the vaccine was applied either by i.p. route (p < 0.006) or by s.c. injection (p < 0.0008). B16 cells expressing mGM-CSF after infection with rvv-mGM-CSF or transduction with a retroviral vector, were equally effective (p > 0.14) as vaccines against lung metastasis. Inhibition of metastasis was also B16 tumor cell specific. These data suggest that this approach of cancer gene therapy has a potential for use in cancer patients.
Department of Obstetrics, University of Kentucky, Lexington 40536-0096, USA.
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D000230:Adenocarcinoma / Q000628:therapy; D000818:Animals; D003110:Colonic Neoplasms / Q000628:therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection; D014616:Vaccinia virus
D016178:Granulocyte-Macrophage Colony-Stimulating Factor