Adenoviral GM-CSF Gene Transduction into Breast Cancer Cells Induced Long-Lasting Antitumor Immunity in Mice.
BACKGROUND: Immunogene therapy is regarded as a novel treatment that overcomes the limitation of preexisting adjuvant therapies and demonstrates the potential for the total elimination of cancer cells by affecting concealed tumor cells. The aim of this study was to examine the enhancement of antitumor immunity of irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced mouse breast cancer cells. METHODS: To study prophylactic vaccine effects, Balb/c mice were vaccinated subcutaneously with saline or irradiated mouse breast cancer cells (BalbMC, 1 x10&sup6; /mouse) infected with or without recombinant adenovirus harboring the GM-CSF gene (Adv/GM-CSF) on day-7. Mice were challenged with parental cells (1x10&sup5;/mouse) on day 0 in the flank opposite the vaccination site. RESULTS: BalbMC cells secreted GM-CSF after infection with Adv/GM-CSF. Vaccination with irradiated GM-CSF-secreting BalbMC completely protected syngeneic mouse challenged with live parental cells. On the other hand, vaccination with irradiated BalbMC protected 60% of mice from tumor development after challenge with parental cells. None of the tumor-free mice initially vaccinated with irradiated GM-CSF-producing BalbMC cells developed tumor upon repeated challenge with parental cells during the entire observation period. CONCLUSION: Our study demonstrated the feasibility of this immunotherapeutic approach as a novel adjuvant therapy after surgery for breast cancer.
Ogawa
T
Department of Surgery 1, Kyushu University Facutly of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kusumoto
M
Mizumoto
K
Sato
N
Tanaka
M