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

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-gamma 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.

• Authors: A Smorlesi, F Papalini, F Orlando, A Donnini, F Re, M Provinciali
• Journal: Gene therapy (Gene Ther) Vol. 12 Issue 17 Pg. 1324-32 (Sep 2005) ISSN: 0969-7128 [Print] England
• PMID: 15944732 (Publication Type: Journal Article)

Chemical References

• 4-amino-alpha,alpha,2-trimethyl-1H-imidazo(4,5-c)quinoline-1-ethanol
• Adjuvants, Immunologic
• Aminoquinolines
• Cancer Vaccines
• Interleukin-2
• Vaccines, DNA
• Interleukin-10
• Interferon-gamma
• Imiquimod

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adoptive Transfer
• Aminoquinolines (administration & dosage)
• Animals
• Cancer Vaccines (administration & dosage)
• Female
• Genes, erbB-2
• Genetic Therapy (methods)
• Imiquimod
• Interferon-gamma (immunology)
• Interleukin-10 (immunology)
• Interleukin-2 (immunology)
• Mammary Neoplasms, Experimental (genetics, immunology, therapy)
• Mice
• Mice, Transgenic
• Models, Animal
• Vaccines, DNA (administration & dosage)