title: Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients.
abstract: BACKGROUND
  We previously reported an HLA-A24-restricted cytotoxic T-cell epitope, Survivin-2B80-88, derived from a splice variant of survivin, survivin-2B. In this report, we show a novel HLA-A24-restricted T-cell epitope, Survivin-C58, derived from a wild type survivin, and compared their immunogenicity in oral cancer patients.
  
  
  METHODS
  By stimulating peripheral blood lymphocytes of HLA-A24-positive cancer patients with Survivin-C58 peptide in vitro, the peptide-specific CTLs were induced. In order to compare the immunogenic potential between C58 peptide and 2B80-88 peptide, peripheral blood T-cells from thirteen HLA-A24-positive oral cancer patients were stimulated with either or both of these two peptides.
  
  
  RESULTS
  Survivin-2B80-88 peptide-specific CTLs were induced from four patients, and C58 peptide-specific CTLs were induced from three out of eight patients with over stage II progression. The CTLs exerted cytotoxicity against HLA-A24-positive tumor cells. In contrast, CTL induction failed from a healthy volunteer and all four patients with cancer stage I.
  
  
  CONCLUSIONS
  It was indicated that a splicing variant-derived peptide and wild type survivin-derived peptide might have a comparable potency of CTL induction, and survivin targeting immunotherapy using survivin-2B80-88 and C58 peptide cocktail should be suitable for HLA-A24+ oral cancer patients.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. jkoba@sapmed.ac.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Satomi
authors.initials: S
authors.lastname: Idenoue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hiratsuka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014018:Tissue Distribution
chemical_list: C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D010455:Peptides; D000077022:Survivin