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Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients
H Shomura1, S Shichijo, S Matsueda
1Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
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.
Insights
Researchers identified two novel epidermal growth factor receptor (EGFR) peptides recognized by immune cells in cancer patients. These peptides show potential for developing new EGFR-targeted immunotherapies for epithelial cancers.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is a key target in epithelial cancer therapy, with existing treatments including antibodies and tyrosine-kinase inhibitors.
- While EGFR-targeted therapies are advancing, there's a need for novel approaches like peptide-based immunotherapies.
- Cytotoxic T lymphocyte (CTL)-directed epitope peptides offer a potential new class of therapeutic compounds.
Purpose of the Study:
- To identify EGFR-derived peptides recognized by both cellular and humoral immunity in HLA-A2(+) epithelial cancer patients.
- To explore the potential of these peptides in developing novel EGFR-targeted cancer therapies.
- To establish a scientific basis for EGFR-based immunotherapy in specific cancer patient populations.
Main Methods:
- Analysis of EGFR-derived peptides for recognition by patient sera (humoral immunity).
- Assessment of peptide ability to induce HLA-A2-restricted peptide-specific CTLs.
- Utilizing peripheral blood mononuclear cells (PBMCs) from epithelial cancer patients.
Main Results:
- Two specific EGFR-derived peptides (positions 479-488 and 1138-1147) were identified.
- These peptides were recognized by the majority of patients' sera (IgG).
- The identified peptides demonstrated the ability to induce HLA-A2-restricted peptide-specific CTLs against EGFR-positive tumor cells.
Conclusions:
- The identified EGFR peptides serve as potential targets for immunotherapy.
- These findings support the development of EGFR-based immunotherapies for HLA-A2(+) cancer patients.
- This study provides a foundation for novel peptide-based cancer treatment strategies targeting EGFR.
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