GENETIC IMMUNOTHERAPY OF ESTABLISHED TUMORS WITH ADENOVIRUS-MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Increased local production of granulocyte-macrophage colony-stimulatin g factor (GM-CSF) by genetically modified tumor cells can induce speci fic antitumor cellular immunity, We constructed a recombinant adenovir us 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 fo rmation in syngenic mice (C57BL/6), and transduced and irradiated Lewi s lung carcinoma cells induced regression of pre-established wild-type tumors without in vitro selection for transductants, Low, but signifi cant, levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice inoculated with GM-CSF but not with reporter virus-tr ansduced 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.