HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties

Vaccine. 2009 Dec 10;28(1):162-70. doi: 10.1016/j.vaccine.2009.09.104. Epub 2009 Sep 30.


The HER-2/neu oncoprotein is a promising cancer vaccine target. We describe herein a novel HLA-A2.1-restricted epitope, encompassing amino acids 657-665 (AVVGILLVV), which is naturally presented by human breast and ovarian cell lines. HER-2/neu(657-665), [HER-2(9(657))], binds with high affinity to HLA-A2.1 molecules as revealed by a prediction algorithm (SYFPEITHI) and in functional assays. This peptide was found to be immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded with increased IFNgamma production, degranulation, and in vitro as well as in vivo cytotoxicity. Most important, HER-2(9(657)) functioned as a therapeutic vaccine by enabling HHD mice to reject established transplantable tumors. Cured mice resisted tumor growth when re-challenged with the same tumor, demonstrating the capacity of HER-2(9(657)) to generate tumor-specific memory immune response. Finally, this peptide was also found to be immunogenic in PBMCs from HLA-A2.1(+) patients with HER-2/neu(+) breast cancer. Our data encourage further exploitation of HER-2(9(657)) as a promising candidate for peptide-based cancer vaccines.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Epitopes / immunology*
  • Female
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / immunology*
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • HLA-A2 Antigen
  • Peptide Fragments
  • Interferon-gamma
  • Receptor, ErbB-2