Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat protoneu by DNA vaccination

S. M. Pupa, A. M. Invernizzi, S. Forti, E. Di Carlo, P. Musiani, P. Nanni, P. L. Lollini, R. Meazza, S. Ferrini, S. Menard

Research output: Contribution to journalArticle

Abstract

The HER-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. The oncogenic potential of HER-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. To test the efficacy of immune-based strategies in eliciting an antitumor response, we used the N#202 transgenic mouse model engineered to overexpress the rat neu proto-oncogene under the control of the mouse mammary tumor virus promoter; females of this line develop spontaneous focal mammary tumors by 6 months of age. Transgenic mice immunized intramuscularly with a HER-2 cDNA ligated into the VR1012 (VICAL) expression vector under the control of the cytomegalovirus promoter developed significantly fewer spontaneous tumors as compared with mice injected with the empty vector (P <0.0001) or not injected (P=0.0006). However this protection was observed only when immunization was started in 3-month-old but not in 6-month-old mice. These data suggest that the xenogeneic HER-2 DNA sequence can break immune tolerance to rat neu in transgenic N#202 mice and induce protective immunity that impairs the neu oncogene-driven progression of mammary carcinogenesis. The preventive effect achieved by our immunological approach appeared not to be based on anti-neu specific B and T cell immune attacks but was more possibly based on different mechanisms including aspecific and inflammatory immunological responses.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalGene Therapy
Volume8
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Breast cancer
  • DNA vaccination
  • Proto-neu-transgenic mice

ASJC Scopus subject areas

  • Genetics

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    Pupa, S. M., Invernizzi, A. M., Forti, S., Carlo, E. D., Musiani, P., Nanni, P., Lollini, P. L., Meazza, R., Ferrini, S., & Menard, S. (2001). Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat protoneu by DNA vaccination. Gene Therapy, 8(1), 75-79. https://doi.org/10.1038/sj.gt.3301360