Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2+ cancer patients
H Shomura, S Shichijo, S Matsueda… - British journal of …, 2004 - nature.com
H Shomura, S Shichijo, S Matsueda, T Kawakami, Y Sato, S Todo, K Itoh
British journal of cancer, 2004•nature.comEpidermal 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) …
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) …
Abstract
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.
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