Insertion of the DNA for the 163-171 peptide of IL1 beta enables a DNA vaccine encoding p185(neu) to inhibit mammary carcinogenesis in Heu-2/neu transgenic BALB/c mice

An assessment was made of the effectiveness of DNA vaccination in preventio n of the mammary adenocarcinomas of BALB/c female mice transgenic for the a ctivated rat Her-2/neu oncogene. Atypical hyperplasia is evident in their m ammary glands when they are 6 weeks old and in situ carcinoma by the 13th w eek. Palpable invasive carcinomas appear around the 17th week and are alway s evident in all 10 glands by the 33rd week. Intramuscular vaccinations wit h 100 mug plasmid DNA encoding the extracellular domain of the Her-2/neu p1 85 (ECD) performed at the 6th, 12th, 18th and 24th week provided no signifi cant protection, whereas those ECD plasmids in which the DNA coding for the immunomodulatory 163-171 (VQGEESNDK) nonapeptide of human IL1 beta (ECD-IL 1 betap) had been inserted both delayed carcinogenesis and reduced tumor mu ltiplicity. This reduction was associated with a marked immune-inflammatory reaction and a conspicuous leukocyte infiltrate located in the stroma surr ounding the hyperplastic mammary ductul-alveolar structures. If was also di rectly correlated with a high anti-p185(neu) antibody production and an imm unoglobulin switch to IgG2a and IgA. No anti-p185(neu) cytotoxic response w as found. No significant protection was obtained when the DNA coding for th e non-active peptide 189-197 of IL1 beta was inserted.