title: 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.affiliation: 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.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Gil
authors.forename: Uk-Hyun
authors.initials: UH
authors.lastname: Jo
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jinho
authors.initials: J
authors.lastname: Kang
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: InSun
authors.initials: I
authors.lastname: Kim
authors.forename: Vy
authors.initials: V
authors.lastname: Phan-Lai
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Kyong Hwa
authors.initials: KH
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014611:Vaccination; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit