A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu-Expressing Tumor in HLA-A2 Transgenic Mice

Clin Cancer Res. 2016 Aug 15;22(16):4133-44. doi: 10.1158/1078-0432.CCR-16-0044. Epub 2016 Mar 22.


Purpose: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B-subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model.

Experimental design: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8(+) T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu.

Results: STxB-E75 synergized with granulocyte macrophage colony-stimulating factors and CpG and proved to be more efficient than the free E75 peptide in the induction of multifunctional and high-avidity E75-specific anti-CD8(+) T cells resulting in a potent tumor protection in HLA-A2 transgenic mice. High expression of HER2/neu inhibited the expression of HLA-class I molecules, leading to a poor recognition of human or murine tumors by E75-specific cytotoxic CD8(+) T cells. In line with these results, STxB-E75 preferentially inhibited the growth of HLA-A2 tumors expressing low levels of Her2/neu. Coadministration of anti-Her2/neu mAb potentiated this effect.

Conclusions: STxB-E75 vaccine is a potent candidate to be tested in patients with low Her2/neu-expressing tumors. It could also be indicated in patients expressing high levels of Her2/neu and low intratumoral T-cell infiltration to boost the recruitment of T cells-a key parameter in the efficacy of anti-Her2/neu mAb therapy. Clin Cancer Res; 22(16); 4133-44. ©2016 AACR.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology*
  • Humans
  • Melanoma, Experimental
  • Mice
  • Mice, Transgenic
  • Neoplasms / genetics*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Xenograft Model Antitumor Assays


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Peptide Fragments
  • ERBB2 protein, human
  • Receptor, ErbB-2