論文 - 詳細
RRC ID | 38185 |
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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) |