title: New polycomb group protein enhancer of zeste homolog (EZH) 2-derived peptide with the potential to induce cancer-reactive cytotoxic T lymphocytes in prostate cancer patients with HLA-A3 supertype alleles.
abstract: Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele(+) prostate cancer patients. As a result, EZH2733-741 peptide was found to efficiently induce peptide-specific CTLs. The EZH2733-741 peptide-stimulated and purified CD8(+) T cells from PBMCs of HLA-A3 supertype allele(+) prostate cancer patients showed higher cytotoxicity against HLA-A3 supertype allele-expressing LNCaP prostate cancer cells than against parental LNCaP cells. This cytotoxicity against HLA-A3 supertype allele-expressing LNCaP cells was partially but significantly inhibited by the addition of EZH2733-741 peptide-pulsed competitive cells. These results indicate that the EZH2733-741 peptide could be a promising candidate for peptide-based immunotherapy for HLA-A3 supertype allele(+) prostate cancer 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 A
authors.initials: MA
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: D000483:Alleles; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000071221:Enhancer of Zeste Homolog 2 Protein; D005434:Flow Cytometry; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D063151:Polycomb Repressive Complex 2 / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014162:Transfection
chemical_list: D019496:Cancer Vaccines; D015791:HLA-A3 Antigen; D010446:Peptide Fragments; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: CTL; EZH2; HLA-A3 supertype allele; Peptide; Prostate cancer