Abstract
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, l×106/mouse) infected with or without recombinant adenovirus harboring the GM-CSF gene (Adv/GM-CSF) on day —7. Mice were challenged with parental cells (1×105/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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- GM-CSF:
-
Granulocyte-macrophage colony-stimulating factor
- MOI:
-
Multiplicity of infection
References
Waki K, Suzuki S, Ohno Y,et al: Epidemiology of breast cancer in Japan.Int J Epidemiol 24:285–291, 1995.
Noguchi M, Taniya T, Kumaki T,et al: Dietary fat and breast cancer; A controversial issue.Breast Cancer 4:67–75, 1997.
Ueji M, Ueno E, Osei-Hiyaman D,et al: Risk factors for breast cancer among Japanese woman; A case-control study in Ibaraki, Japan.Breast Cancer 5:351–358, 1998.
Gordon A: The increasing efficacies of breast cancer treatment.Clin Oncol 9:338–342, 1997.
Metcalf D: The granulocyte-macrophage colony stimulating factor.Science 229:16–22, 1985.
Chen GH, Curtis JL, Mody CH,et al: Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro.J Immunol 152:724–734, 1994.
Bernasconi S, Matteucci C, Sironi M,et al: Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression of adhesion molecules and pro-duction of cytokines in blood monocytes and ovarian cancer-associated macrophages.Int J Cancer 60:300, 1995.
Larsen CP, Ritchie SC, Hendrix R,et al: Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells.J Immunol 152:5208–5219, 1994.
Huang AY, Golumbek P, Ahmadzadeh M,et al: Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens.Science 264:961–965, 1994.
Nagai E, Ogawa T, Kielian T,et al: Irradiated tumor cells adenovirally engineered to secrete granulo-cyte/macrophage-colony-stimulating factor establish antitumor immunity and eliminate pre-existing tumors in syngeneic mice.Cancer Immunol Immuno-ther 47:72–80, 1998.
Lee C, Wu S, Ciernik IF,et al: Genetic immuno-therapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor.Human Gene Ther 8:187–193, 1997.
Abe J, Wakimoto H, Yoshida Y,et al: Antitumor effect induced by granulocyte/macrophage-colony-stimulat-ing factor gene-modified tumor vaccination; Com-parison of adenovirus-and retrovirus-mediated genet-ic transduction.J Cancer Res 121:587–592, 1995.
Dranoff G, Jaffee E, Lazenby A,et al: Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.Proc Natl Acad Sci USA 90:3539–3543, 1993.
Top FH Jr, Buscher EL, Brancroft WH,et al: Immunization with live types 7 and 4 adenovirus vac-cines II; Antibody response and protective effect against acute respiratory disease.J Infect Dis 124:148–154, 1971.
Author information
Authors and Affiliations
About this article
Cite this article
Ogawa, T., Kusumoto, M., Mizumoto, K. et al. Adenoviral GM-CSF gene transduction into breast cancer cells induced long-lasting antitumor immunity in mice. Breast Cancer 6, 301–304 (1999). https://doi.org/10.1007/BF02966444
Issue Date:
DOI: https://doi.org/10.1007/BF02966444