Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer

Br J Cancer. 2011 Jan 18;104(2):300-7. doi: 10.1038/sj.bjc.6606052. Epub 2010 Dec 21.

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.

Conclusion: KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Epitopes / chemistry
  • Epitopes / immunology*
  • HLA-A2 Antigen / chemistry
  • HLA-A2 Antigen / immunology*
  • Humans
  • Immunohistochemistry
  • Kinesin / immunology*
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • DNA Primers
  • Epitopes
  • HLA-A2 Antigen
  • KIF20A protein, human
  • Kinesin