Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice

An Erratum to this article was published on 18 February 2016

Abstract

ErbB-2 has been implicated as a target for cancer-initiating cells in breast and other cancers. ErbB-2-directed peptide vaccines have been shown to be effective in prevention of spontaneous tumorigenesis of breast in neu transgenic mouse model, and cellular immunity is proposed as a mechanism for the anti-tumor efficacy. However, there has been no explanation as to how immunity suppresses tumorigenesis from the early stage carcinogenesis, when ErbB-2 expression in breast is low. Here, we investigated a peptide-based vaccine, which consists of two MHC class II epitopes derived from murine ErbB-2, to prevent the occurrence of spontaneous tumors in breast and assess immune impact on breast cancer stem cells. Female MMTV-PyMT transgenic mice were immunized with either ErbB-2 peptide vaccine, or a peptide from tetanus toxoid, or PBS in immune adjuvant. ErbB-2 peptides vaccine completely suppressed spontaneous breast tumors, and the efficacy was correlated with antigen-specific T-cell and antibody responses. In addition, immune serum from the mice of ErbB-2 vaccine group had an inhibitory effect on mammosphere-forming capacity and signaling through ErbB-2 and downstream Akt pathway in ErbB-2 overexpressing mouse mammary cancer cells. We provide evidence that multi-epitope class II peptides vaccine suppresses tumorigenesis of breast potentially by inhibiting the growth of cancer stem cells. We also suggest that a strategy of inducing strong immune responses using multi-epitope ErbB-2-directed helper vaccine might be useful in preventing breast cancer recurrence.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2009-0068859). MLD is supported by the Athena Distinguished Professor of Breast Cancer Research.

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The authors declare that they have no conflict of interest.

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Correspondence to Kyong Hwa Park.

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Gil, EY., Jo, UH., Lee, H.J. et al. Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice. Breast Cancer Res Treat 147, 69–80 (2014). https://doi.org/10.1007/s10549-014-3086-4

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Keywords

  • Breast cancer
  • ErbB-2
  • Peptide vaccine
  • Cancer stem cell
  • Spontaneous tumor