Identification and characterization of a HER-2/neu epitope as a potential target for cancer immunotherapy

Cancer Immunol Immunother. 2010 May;59(5):715-27. doi: 10.1007/s00262-009-0791-7. Epub 2009 Nov 11.


Our aim is to develop peptide vaccines that stimulate tumor antigen-specific T-lymphocyte responses against frequently detected cancers. We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines. HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay. This peptide was stable for 3.5 h in an off-kinetic assay. HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity. Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients. Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201. Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice. Our data encourage further exploitation of HER-2(9(828)) as a promising candidate for peptide-based cancer vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / immunology
  • Cancer Vaccines / immunology*
  • Cell Separation
  • Epitopes, T-Lymphocyte / immunology*
  • Flow Cytometry
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • Humans
  • Immunotherapy / methods*
  • Mice
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Peptide Fragments
  • Receptor, ErbB-2