Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial

Cancer. 2006 Jun 1;106(11):2309-17. doi: 10.1002/cncr.21849.


Background: E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I-->V at position 2, 2VGP2) associated with increased breast cancer risk was addressed.

Methods: Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75+GP2.

Results: GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2- control target SKOV3 of 28.8+/-3.7% (P<.01), 29.5+/-4.0% (P<.01), and 16.9+/-2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8+/-5.2% versus 44.2+/-5.7% for E75 (P=.87). When combined, an additive effect was noted with 58.6+/-5.4% lysis (P=.05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6+/-5.7%) and 2VGP2-loaded T2 targets (17.7+/-5.2%).

Conclusions: GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Chromium / metabolism
  • Dendritic Cells / immunology
  • Epitopes / immunology
  • Female
  • Humans
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy
  • Peptide Fragments / immunology*
  • Peptide Fragments / therapeutic use
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Tissue Donors
  • Tumor Cells, Cultured


  • Cancer Vaccines
  • Epitopes
  • HER-2 peptide E75 (369-377), human
  • HER2-neu-derived peptide (654-662)
  • Peptide Fragments
  • Chromium
  • Receptor, ErbB-2