Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients.
Epidermal growth factor receptor (EGFR) is one of the most appropriate target molecules for cancer therapy because of its relatively high expression in about one-third of all epithelial cancers in correlation with neoplasmic progression. With respect to EGFR-targeted therapies, antibodies and tyrosine-kinase inhibitors have been intensively studied, a novel EGFR-tyrosine-kinase inhibitor ZD1839 has been approved as an anticancer drug, and many other agents are now under clinical trial. In addition, cytotoxic T lymphocyte (CTL)-directed epitope peptides could be another class of compounds useful in EGFR-targeted therapies. However, there is presently no information on CTL-directed peptides of EGFR. Therefore, from the viewpoint of development of peptide-based cancer therapy, this study was intended to determine the EGFR-derived peptides recognised by both cellular and humoral immunities in HLA-A2(+) epithelial cancer patients. We herein report finding of two such types of EGFR-derived peptides at position 479-488 and 1138-1147, both of which were recognised by the majority of patients' sera (IgG), and also possessed the ability to induce HLA-A2-restricted peptide-specific CTLs against EGFR-positive tumour cells in peripheral blood mononuclear cells (PBMCs) of epithelial cancer patients. These results may provide a scientific basis for the development of EGFR-based immunotherapy for HLA-A2(+) cancer patients.
Shomura
H
H
Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Shichijo
S
S
Matsueda
S
S
Kawakami
T
T
Sato
Y
Y
Todo
S
S
Itoh
K
K
D000917:Antibody Formation; D019496:Cancer Vaccines / Q000276:immunology*; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis / Q000502:physiology*; D015789:HLA-A2 Antigen / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology
D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D010455:Peptides; D066246:ErbB Receptors