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

Eun Young Gil, Uk Hyun Jo, Hye Jin Lee, Jinho Kang, Jae Hong Seo, Eun Sook Lee, Yeul Hong Kim, Insun Kim, Vy Phan-Lai, Mary L. Disis, Kyong Hwa Park

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalBreast Cancer Research and Treatment
Volume147
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Neoplastic Stem Cells
Subunit Vaccines
Transgenic Mice
Vaccination
Breast Neoplasms
Peptides
Carcinogenesis
Epitopes
Neoplasms
Breast
Vaccines
Tetanus Toxoid
Cellular Immunity
Antibody Formation
Immune Sera
Immunity
T-Lymphocytes
Antigens
Recurrence
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice. / Gil, Eun Young; Jo, Uk Hyun; Lee, Hye Jin; Kang, Jinho; Seo, Jae Hong; Lee, Eun Sook; Kim, Yeul Hong; Kim, Insun; Phan-Lai, Vy; Disis, Mary L.; Park, Kyong Hwa.

In: Breast Cancer Research and Treatment, Vol. 147, No. 1, 01.01.2014, p. 69-80.

Research output: Contribution to journalArticle

Gil, Eun Young ; Jo, Uk Hyun ; Lee, Hye Jin ; Kang, Jinho ; Seo, Jae Hong ; Lee, Eun Sook ; Kim, Yeul Hong ; Kim, Insun ; Phan-Lai, Vy ; Disis, Mary L. ; Park, Kyong Hwa. / Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice. In: Breast Cancer Research and Treatment. 2014 ; Vol. 147, No. 1. pp. 69-80.
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