HER-2/neu-derived peptide 884-899 is expressed by human breast, colorectal and pancreatic adenocarcinomas and is recognized by in-vitro-induced specific CD4(+) T cell clones.

Abstract

HER-2/neu peptides recognized in the context of HLA-DR molecules by CD4(+) Th lymphocytes on antigen-presenting cells have been identified. In this report, we demonstrate for the first time that HER-2/neu helper epitopes are also expressed on the surface of metastatic breast, colorectal and pancreatic carcinomas. Peripheral blood mononuclear cells from an HLA-DR4 healthy donor were used to induce HER-2/neu peptide-specific CD4(+) T cell clones by in vitro immunization with HER-2/neu peptide (884-899)-pulsed autologous dendritic cells (DCs). Strong proliferation and significant levels of IFN-gamma were induced by the CD4(+) T cell clones in response to specific stimulation with autologous DCs loaded with HER-2(884-899). Furthermore, these clones also recognized HER-2/neu(+) tumor cell lines, and tumor cells from breast, colorectal and pancreatic adenocarcinomas induced to express HLA-DR4, but also the HLA-DR4(+) melanoma cell line FM3 transfected to express HER-2/neu. The recognition of tumor cells was strongly inhibited by an anti-HLA-DR mAb. Taken altogether, we provide novel information for the role of HER-2(884-899) as a naturally processed epitope expressed by breast, colorectal and pancreatic carcinomas and the capacity of HER-2/neu protein to follow the endogenous class II processing pathway. Our results suggest that HER-2(884-899) might be attractive for broadly applicable vaccines and may prove useful for adoptive immunotherapy designed for breast, colorectal and pancreatic carcinomas.

• Authors: Sonia A Perez, Panagiota A Sotiropoulou, Nectaria N Sotiriadou, Avgi Mamalaki, Angelos D Gritzapis, Hartmut Echner, Wolfgang Voelter, Graham Pawelec, Michael Papamichail, Constantin N Baxevanis
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 50 Issue 11 Pg. 615-24 (Jan 2002) ISSN: 0340-7004 [Print] Germany
• PMID: 11807625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• HER-2-derived peptide 884-899
• Peptide Fragments
• Receptor, ErbB-2

Topics

• Adenocarcinoma (immunology, pathology)
• Antigen Presentation
• Antigens, Neoplasm (immunology)
• Breast Neoplasms (immunology, pathology)
• CD4-Positive T-Lymphocytes (immunology)
• Colorectal Neoplasms (immunology, pathology)
• Cytotoxicity, Immunologic
• Dendritic Cells (immunology)
• Female
• Humans
• Immunotherapy, Adoptive
• Pancreatic Neoplasms (immunology, pathology)
• Peptide Fragments (immunology)
• Receptor, ErbB-2 (immunology)
• Tumor Cells, Cultured