title: Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer.
abstract: BACKGROUND
  Identification of tumour-associated antigens (TAAs) that induce cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the development of anticancer immunotherapy. In this study, we aimed at identifying a novel TAA of pancreatic cancer for immunotherapy.
  
  
  METHODS
  On the basis of the genome-wide cDNA microarray analysis, we focused on KIF20A (also known as RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2 (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2 transgenic mice (Tgm) and the peptides were examined to check whether they could generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+) tumour cells in vitro.
  
  
  RESULTS
  KIF20A was overexpressed in pancreatic cancer and in some other malignancies, but not in their non-cancerous counterparts and many normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809-817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA-A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+) healthy donors by in vitro stimulation with the three peptides, and those CTLs successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A and HLA-A2.
  
  
  CONCLUSIONS
  KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: S
authors.initials: S
authors.lastname: Hirata
authors.forename: A
authors.initials: A
authors.lastname: Irie
authors.forename: S
authors.initials: S
authors.lastname: Senju
authors.forename: Y
authors.initials: Y
authors.lastname: Ikuta
authors.forename: K
authors.initials: K
authors.lastname: Yokomine
authors.forename: M
authors.initials: M
authors.lastname: Harao
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Tsunoda
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D017931:DNA Primers; D000939:Epitopes; D015789:HLA-A2 Antigen; C410089:KIF20A protein, human; D016547:Kinesins