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Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma

Gene Therapy volume 12, pages 1324–1332 (2005)Cite this article

Abstract

DNA vaccination against HER-2/neu is an effective way to induce an immune response able to oppose the spontaneous development of mammary tumours occurring in HER-2/neu transgenic mice. In this study, we have evaluated the potential of Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER-2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of rat HER2/neu with either Imiquimod or S-27609 was found to delay the development of spontaneous mammary tumours and to reduce their incidence, in comparison with DNA vaccination alone. Almost 80 or 40% of tumour-free mice were found at the end of measurement time in mice vaccinated and supplemented with Imiquimod or S-27609, respectively. The antitumour preventive effect was associated with increased antibody and cell-mediated immune responsiveness against HER-2/neu. In mice vaccinated and supplemented with Imiquimod, a small but significant increase of rat p185neu-specific cytotoxicity and of IFN-γ and IL-2-producing CD8T cells, together with a reduction of IL-4-producing CD4T cells, and a switch from an IgG1 towards a IgG2a phenotype of anti-p185neu antibodies, suggested a TH1 polarization of the immune response. The immunoregulatory efficacy of S-27609 was lower than that observed for Imiquimod. These data highlight the potential of Imiquimod, and, to a lower extent, of S-27609, as immunological adjuvants of therapeutic DNA vaccines.

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Authors and Affiliations

  1. INRCA Research Department, Laboratory of Tumor Immunology, Immunology Center, Ancona, Italy

    A Smorlesi, F Papalini, A Donnini, F Re & M Provinciali

  2. INRCA Research Department, Experimental Animal Models for Aging Unit, Ancona, Italy

    F Orlando & M Provinciali

Authors
  1. A Smorlesi
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  2. F Papalini
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  3. F Orlando
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  4. A Donnini
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  5. F Re
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  6. M Provinciali
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Smorlesi, A., Papalini, F., Orlando, F. et al. Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine model of HER2/neu-positive mammary carcinoma. Gene Ther 12, 1324–1332 (2005). https://doi.org/10.1038/sj.gt.3302559

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  • DOI: https://doi.org/10.1038/sj.gt.3302559

Keywords

  • Imiquimod
  • DNA vaccination
  • HER-2/neu
  • adjuvants
  • toll-like receptors
  • transgenic mice

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