Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor.
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| Abstract |
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.
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| Authors | C T Lee, S Wu, I F Ciernik, H Chen, S Nadaf-Rahrov, D Gabrilovich, D P Carbone |
| Journal | Human gene therapy (Hum Gene Ther) Vol. 8 Issue 2 Pg. 187-93 (Jan 20 1997) ISSN: 1043-0342 [Print] United States |
| PMID | 9017422 (Publication Type: Journal Article) |
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