Targeting HER-2/neu for active-specific immunotherapy in a mouse model of spontaneous breast cancer

Int J Cancer. 1999 Oct 29;83(3):393-400. doi: 10.1002/(sici)1097-0215(19991029)83:3<393::aid-ijc16>;2-m.


The identification of tumor-associated antigens has led to increased interest in vaccination strategies to treat and/or prevent cancer. This study examined the feasibility of active-specific immunotherapy against the breast-tumor antigen HER-2/neu using a HER-2/neu transgenic (rNeu-TG) mouse model. rNeu-TG mice develop spontaneous breast tumors after pregnancy, indicating that they fail to mount an effective immune response against rNeu. Allogeneic fibroblasts expressing HER-2/neu were used as a cell-based vaccine. Vaccination induced a rNeu-specific anti-tumor immune response that prevented tumor formation of transplanted breast-tumor cells, and also protected mice from spontaneous tumor formation. Both T-cell-mediated and humoral immune responses were detectable in vaccinated mice. Vaccination also protected tumor-bearing mice from a challenge with cell suspensions isolated from spontaneous tumors, indicating that rNeu-TG mice are not tolerant to rNeu, even after spontaneous tumor formation. However, established spontaneous tumors themselves were never affected. This observation correlated with T-cell infiltrations in the injected but not in the established spontaneous tumor. Thus, allogeneic fibroblasts are efficient vaccine vectors to prime a specific immune response against an over-expressed tumor antigen. Moreover, our results suggest striking differences in the immunological requirements for the rejection of an established vs. a transplanted tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Neoplasm / biosynthesis
  • CD3 Complex / analysis
  • Female
  • Graft Rejection
  • Mammary Neoplasms, Animal / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes / immunology
  • Vaccination*


  • Antibodies, Neoplasm
  • CD3 Complex
  • Receptor, ErbB-2