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

Gene Ther. 2001 Jan;8(1):75-9. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cancer Vaccines*
  • Cytotoxicity, Immunologic
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Immunization Schedule
  • Lymphocyte Culture Test, Mixed
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / prevention & control*
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Rats
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism*
  • Vaccines, DNA*


  • Cancer Vaccines
  • Neoplasm Proteins
  • Vaccines, DNA
  • Receptor, ErbB-2