title: Identification of erythropoietin receptor-derived peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes from HLA-A24(+) patients with renal cell carcinoma.
abstract: Molecular targeting therapy with anti-angiogenic agents, including sunitinib and sorafenib, has been proven to be the first- and second-line standard treatments for metastatic renal cell carcinoma (mRCC) worldwide. Despite their significant antitumor effects, most of the patients with mRCC have not been cured. Under such circumstances, anti-cancer immunotherapy has been considered as a promising treatment modality for mRCC, and cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells and molecules. Therefore, we previously conducted anti-cancer vaccine therapy with peptides derived from carbonic anhydrase-9 and vascular endothelial growth factor receptor-1 as phase-I/II trials for mRCC patients and reported their clinical benefits. Alternatively, up-regulated expression of erythropoietin (Epo) and its receptor (EpoR) in RCC has been reported, and their co-expression is involved in tumorigenesis. In order to increase options for peptide-based vaccination therapy, we searched for novel EpoR-peptides for HLA-A24(+) RCC patients. Among 5 peptides derived from EpoR, which were prepared based on the binding motif to the HLA-A24 allele, EpoR52-60 peptide had the potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Cytotoxicity toward HLA-A24(+) and EpoR-expressing RCC cells was ascribed to peptide-specific CD8(+) T cells. These results indicate that the EpoR52-60 peptide could be a promising candidate for a peptide-based anti-cancer vaccine for HLA-A24(+) mRCC patients.
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan. Electronic address: minami@med.kindai.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Marco
authors.initials: M
authors.lastname: De Velasco
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Immunology, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Nanae
authors.initials: N
authors.lastname: Harashima
authors.affiliation: Department of Immunology, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Urology, Kinki University School of Medicine, Osaka, Japan. Electronic address: huemura@med.kindai.ac.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
mesh_terms: D019496:Cancer Vaccines; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D059871:HLA-A24 Antigen / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D059871:HLA-A24 Antigen; D010455:Peptides; D017467:Receptors, Erythropoietin
keywords: CTL; Erythropoietin receptor; Peptide; Renal cell carcinoma