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1
* Molecular Targeting Unit,
Melanoma Genetics Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy; and
Department of Human Anatomy,
Institute of Pathology, University of Milan, 20133 Milan, Italy
1Correspondence: Chair of Immunology c/o Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. E-mail: balsari{at}istitutotumori.mi.it
Unmethylated CpG-oligodeoxynucleotides (CpG-ODNs) are recognized as a ‘danger signal’ and are potent immunostimulators. To test whether tumors might be prevented by maintaining the innate immune system on continuous alert, proto-neu transgenic female mice, which develop spontaneous mammary tumors, were systemically treated with CpG-ODNs at 10-day intervals. Tumor incidence and number of tumors/mouse were significantly lower in treated mice compared with the control group. Moreover, CpG-ODN systemic treatment significantly reduced lung metastases induced by intravenous inoculation of N202.1A cells derived from a spontaneous mammary carcinoma. Growth of established tumors was modestly inhibited after CpG-ODN systemic treatment but strongly on peritumoral application. Our data indicate that systemic repeated injection of CpG-ODN to maintain the innate immune system on continuous alert prevents the onset of genetically determined tumors and confers tumor protection when the tumor load is low.—Sfondrini, L., Besusso, D., Rumio, C., Rodolfo, M., Ménard, S., Balsari, A. Prevention of spontaneous mammary adenocarcinoma in HER-2/neu transgenic mice by foreign DNA.
Key Words: murine tumors • CpG-oligodeoxynucleotides • danger signal • innate immunity
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