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.
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.
Perez
Sonia A
SA
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, 171 Alexandras Avenue, 115 22 Athens, Greece.
Sotiropoulou
Panagiota A
PA
Sotiriadou
Nectaria N
NN
Mamalaki
Avgi
A
Gritzapis
Angelos D
AD
Echner
Hartmut
H
Voelter
Wolfgang
W
Pawelec
Graham
G
Papamichail
Michael
M
Baxevanis
Constantin N
CN
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C445779:HER-2-derived peptide 884-899