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  • Acquired Diseases
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DNA vaccination with full-length or truncated Neu induces protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice

Gene Therapy volume 7, pages 703–706 (2000)Cite this article

Abstract

Genetic immunization against tumor antigens is an effective way to induce an immune response able to oppose cancer progression. Overexpression of HER-2/neu can lead to neoplastic transformation and has been found in many human primary breast cancers. We constructed DNA expression vectors encoding the full-length neu oncogene of rat cDNA (pCMV-NeuNT), the neu extracellular domain (pCMV-ECD), or the neu extracellular and transmembrane domains (pCMV-ECD-TM). We evaluated whether i.m. injection of these plasmids induces protection against the development of mammary tumors occurring spontaneously in FVB/N neu-transgenic mice. We found that pCMV-ECD-TM induced the best protection, whereas both pCMV-ECD and pCMV-NeuNT were less effective. The coinjection with a bicistronic vector for murine IL-12 increased the efficacy of pCMV-ECD and pCMV-NeuNT plasmids, and led to the same protection obtained with pCMV-ECD-TM alone. Anti-neuECD antibodies were detected in pCMV-ECD-TM vaccinated mice and, after coinjection with pCMV-IL12 plasmids, they appeared also in animals immunized with pCMV-ECD. Our data demonstrate the effectiveness of DNA vaccination using truncated Neu plasmids in inducing antitumor protection in a spontaneous mammary tumor model.

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Acknowledgements

This work was supported by Associazone Italiana per la Ricerca sul Cancro (AIRC) and by INDENA SpA, Milano. We thank Professor G Forni of the Department of Clinical and Biological Sciences, University of Torino, Dr E Balducci of the Department of Morphological Sciences and Comparative Biochemistry, University of Camerino and Dr R Salvi of the CHUV-Nestlé of Lausanne for their helpful discussions.

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Authors and Affiliations

  1. Department of Biology MCA, General Physiology (Laboratory of Genetic Immunization), University of Camerino, Camerino, Italy

    A Amici, A Smorlesi, P Cappelletti, L Capparuccia, R Coppari, R Lucciarini & C Petrelli

  2. INRCA Research Department, Biotechnology Center, Ancona, Italy

    G Noce

  3. Department of Pharmacological Sciences and Experimental Medicine, Laboratory of General Pathology, University of Camerino, Camerino, Italy

    G Santoni

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

    M Provinciali

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  1. A Amici
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Amici, A., Smorlesi, A., Noce, G. et al. DNA vaccination with full-length or truncated Neu induces protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Gene Ther 7, 703–706 (2000). https://doi.org/10.1038/sj.gt.3301151

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