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Insertion of the DNA for the 163–171 peptide of IL1β enables a DNA vaccine encoding p185neu to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice

Gene Therapy volume 8, pages 447–452 (2001)Cite this article

Abstract

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 μg 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 IL1β (ECD-IL1βp) 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-p185neu antibody production and an immunoglobulin switch to IgG2a and IgA. No anti-p185neu cytotoxic response was found. No significant protection was obtained when the DNA coding for the non-active peptide 189–197 of IL1β was inserted.

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Acknowledgements

We thank Dr John Iliffe for critical review of the manuscript. This work was supported by the Italian Association for Cancer Research, the Istituto Superiore di Sanità, Special project gene therapy, CNR Target project on Biotechnology, Ministero dell'Università e della Ricerca Scientifica, and by the Department of Army, USA, Grant DAMD17–98–1-8030 (to Guido Forni). The information contained in this paper does not necessarily reflect the position or the policy of the US government, and no official endorsement should be inferred.

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Authors and Affiliations

  1. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    S Rovero, K Boggio, E Quaglino, P Porcedda & G Forni

  2. Department of Patological Anatomy, G D'Annunzio University, Chieti, Italy

    E Di Carlo & P Musiani

  3. Department of Biology MCA, University of Camerino, Camerino, Italy

    A Amici

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  1. S Rovero
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Rovero, S., Boggio, K., Carlo, E. et al. Insertion of the DNA for the 163–171 peptide of IL1β enables a DNA vaccine encoding p185neu to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice. Gene Ther 8, 447–452 (2001). https://doi.org/10.1038/sj.gt.3301416

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