Prevention of spontaneous mammary adenocarcinoma in HER-2/neu transgenic mice by foreign DNA.
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
Lucia
L
Molecular Targeting Unit, Melanoma Genetics Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy.
Besusso
Dario
D
Rumio
Cristiano
C
Rodolfo
Monica
M
Ménard
Sylvie
S
Balsari
Andrea
A
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D009838:Oligodeoxyribonucleotides; D018719:Erb-b2 Receptor Tyrosine Kinases; C408982:CPG-oligonucleotide