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

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.

• Authors: 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 147 Issue 1 Pg. 69-80 (Aug 2014) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 25104444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Vaccines, Subunit
• Receptor, ErbB-2

Topics

• Animals
• Blotting, Western
• Cancer Vaccines (therapeutic use)
• Cell Transformation, Neoplastic (drug effects, immunology, pathology)
• Female
• Humans
• Immunoprecipitation
• Mammary Neoplasms, Experimental (immunology, pathology, prevention & control)
• Mammary Tumor Virus, Mouse (genetics)
• Mice
• Mice, Transgenic
• Neoplastic Stem Cells (drug effects, immunology, pathology)
• Receptor, ErbB-2 (immunology)
• Signal Transduction
• Tumor Cells, Cultured
• Vaccination
• Vaccines, Subunit (therapeutic use)