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

Breast Cancer Research and Treatment volume 147, pages 69–80 (2014)Cite this article

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.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Oncology/Hematology, Departments of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-Gu, Seoul, 136-705, Republic of Korea

    Eun-Young Gil, Uk-Hyun Jo, Hye Jin Lee, Jinho Kang, Jae Hong Seo, Yeul Hong Kim & Kyong Hwa Park

  2. Departments of Pathology, College of Medicine, Korea University, Seoul, Republic of Korea

    InSun Kim

  3. Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea

    Eun Sook Lee

  4. Center for Global Mentoring, UCLA-DOE Institute, University of California Los Angeles, Los Angeles, CA, USA

    Vy Phan-Lai

  5. Tumor Vaccine Group, University of Washington, Seattle, WA, USA

    Mary L. Disis

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  1. Eun-Young Gil
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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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  • DOI: https://doi.org/10.1007/s10549-014-3086-4

Keywords

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