title: A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins.
abstract: We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report, we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of HLA-A24(+) cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24(+) cancer patients.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17 Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Idenoue
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hariu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kurotaki
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tsuruma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Kiyoteru
authors.initials: K
authors.lastname: Kashiwagi
authors.forename: Minoru
authors.initials: M
authors.lastname: Okazaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Tousei
authors.initials: T
authors.lastname: Ohmura
authors.forename: Fumitake
authors.initials: F
authors.lastname: Hata
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology*; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins; D009842:Oligopeptides / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009842:Oligopeptides; D000077022:Survivin