Insertion of the DNA for the 163-171 peptide of IL1beta enables a DNA vaccine encoding p185(neu) to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice.
An assessment was made of the effectiveness of DNA vaccination in prevention of the mammary adenocarcinomas of BALB/c female mice transgenic for the activated rat Her-2/neu oncogene. Atypical hyperplasia is evident in their mammary glands when they are 6 weeks old and in situ carcinoma by the 13th week. Palpable invasive carcinomas appear around the 17th week and are always evident in all 10 glands by the 33rd week. Intramuscular vaccinations with 100 microg plasmid DNA encoding the extracellular domain of the Her-2/neu p185 (ECD) performed at the 6th, 12th, 18th and 24th week provided no significant protection, whereas those ECD plasmids in which the DNA coding for the immunomodulatory 163-171 (VQGEESNDK) nonapeptide of human IL1beta (ECD-IL1betap) had been inserted both delayed carcinogenesis and reduced tumor multiplicity. This reduction was associated with a marked immune-inflammatory reaction and a conspicuous leukocyte infiltrate located in the stroma surrounding the hyperplastic mammary ductul-alveolar structures. It was also directly correlated with a high anti-p185(neu) antibody production and an immunoglobulin switch to IgG2a and IgA. No anti-p185(neu) cytotoxic response was found. No significant protection was obtained when the DNA coding for the non-active peptide 189-197 of IL1beta was inserted.
Rovero
S
S
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Boggio
K
K
Di Carlo
E
E
Amici
A
A
Quaglino
E
E
Porcedda
P
P
Musiani
P
P
Forni
G
G
D000818:Animals; D000906:Antibodies / Q000097:blood; D005260:Female; D018734:Genes, erbB-2 / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D007375:Interleukin-1 / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051381:Rats; D018709:Statistics, Nonparametric; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000906:Antibodies; D007375:Interleukin-1; D019444:Vaccines, DNA