Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor

Hum Gene Ther. 1997 Jan 20;8(2):187-93. doi: 10.1089/hum.1997.8.2-187.


Increased local production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by genetically modified tumor cells can induce specific antitumor cellular immunity. We constructed a recombinant adenovirus expressing murine GM-CSF and tested it for therapeutic efficacy in a syngeneic murine lung cancer model system. In vitro transduction of Lewis lung carcinoma cells with adenovirus-mGM-CSF suppressed tumor formation in syngenic mice (C57BL/6), and transduced and irradiated Lewis lung carcinoma cells induced regression of pre-established wild-type tumors without in vitro selection for transductants. Low, but significant, levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice inoculated with GM-CSF but not with reporter virus-transduced tumor cells. GM-CSF-transduced cells induced the accumulation of dendritic cells at the site of tumor, consistent with a mechanism involving improved tumor antigen presentation. These data suggest that transduction of tumor cells with recombinant GM-CSF adenovirus may be an effective and practical cancer gene therapeutic strategy.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / radiotherapy
  • Carcinoma, Lewis Lung / therapy*
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology
  • Disease Models, Animal
  • Female
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Immunotherapy / methods*
  • Mice
  • Mice, Inbred C57BL
  • Recombination, Genetic
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / physiology
  • Transduction, Genetic


  • Granulocyte-Macrophage Colony-Stimulating Factor