title: Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer.
abstract: ERas is a recently identified oncogene involved in the tumorgenic growth of embryonic stem cells. We examined the significance of ERas expression in scirrhous gastric carcinoma, and the possibility of ERas as a tumor-associated antigen of gastric cancer for developing a cancer vaccine. ERas expression was determined in scirrhous gastric carcinoma specimens by immunohistochemical staining. To assess the possibility of the ERas protein as an anticancer vaccine target, we examined whether ERas for HLA-A-restricted epitope peptides were capable of eliciting cytotoxic T lymphocyte activity. Immunohistochemical analysis identified ERas protein in the nucleus and cytoplasm of cancer cells, yet ERas was not expressed in normal gastric epithelium. By western blotting, lysates of the scirrhous gastric cancer cell lines, OCUM-8, OCUM-2MD3 and OCUM-2M were shown to contain a 25-kDa band of ERas protein. ERas mRNA was detected in these cell lines by RT-PCR. To investigate cytotoxicity, we successfully established cytotoxic T lymphocyte clones stimulated by HLA-A*2402-restricted ERas peptides (FALDDPSSL). These peptides have specific cytotoxicity against corresponding HLA-A*2402-positive target cells pulsed with the candidate peptide. We found that the cytotoxic T lymphocyte clones demonstrated cytotoxic activity against OCUM-8 cells that endogenously express ERas. Our results suggest that ERas is a novel tumor-associated antigen with the potential application to be a vaccine against scirrhous gastric cancer.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Iwauchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Yamazoe
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Mami
authors.initials: M
authors.lastname: Yoshii
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kubo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Muguruma
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D002293:Adenocarcinoma, Scirrhous / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism*; D059871:HLA-A24 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D009857:Oncogenes; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; C474774:ERas protein, human; D000939:Epitopes; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; D007371:Interferon-gamma; D015689:Oncogene Protein p21(ras)