Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor.
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.
Lee
C T
CT
Vanderbilt Cancer Center, Venderbilt University School of Medicine, Nashville, TN 37232-6838, USA.
Wu
S
S
Ciernik
I F
IF
Chen
H
H
Nadaf-Rahrov
S
S
Gabrilovich
D
D
Carbone
D P
DP
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology; D014161:Transduction, Genetic
D016178:Granulocyte-Macrophage Colony-Stimulating Factor