RRC ID 38185
著者 Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, Harao M, Inoue M, Tomita Y, Tsunoda T, Nakagawa H, Nakamura Y, Baba H, Nishimura Y.
タイトル Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer.
ジャーナル Br J 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.
CONCLUSION:KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.
巻・号 104(2)
ページ 300-7
公開日 2011-1-18
DOI 10.1038/sj.bjc.6606052
PII 6606052
PMID 21179034
PMC PMC3031900
MeSH Amino Acid Sequence Animals Base Sequence Blotting, Western DNA Primers Epitopes / chemistry Epitopes / immunology* HLA-A2 Antigen / chemistry HLA-A2 Antigen / immunology* Humans Immunohistochemistry Kinesins / immunology* Mice Mice, Knockout Molecular Sequence Data Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms / immunology* Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Cytotoxic / immunology*
IF 5.791
引用数 43
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 T2(RCB1932)