論文

査読有り
2009年11月

The shared tumor associated antigen cyclin-A2 is recognized by high-avidity T-cells

INTERNATIONAL JOURNAL OF CANCER
  • Eisei Kondo
  • ,
  • Britta Maecker
  • ,
  • Andreas Draube
  • ,
  • Nela Klein-Gonzalez
  • ,
  • Alexander Shimabukuro-Vornhagen
  • ,
  • Joachim L. Schultze
  • ,
  • Michael S. von Bergwelt-Baildon

125
10
開始ページ
2474
終了ページ
2478
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/ijc.24629
出版者・発行元
WILEY-LISS

Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclin-specific T cells are considered to be thymically deleted. We identified at least one nonameric HLA-A*0201 binding cyclin-A2 epitope by a reverse immunology approach. Using a highly efficient T-cell expansion system that is based on CD40-activated B (CD40-B) cells as sole antigen-presenting cells we successfully generated cyclin-A2 specific CTL from HLA-A*0201(+) donors. Interestingly, high-avidity cyclin-A2 specific CTL lines, which recognized peptide-pulsed and antigen expressing target cells, were indeed generated by stimulation with CD40-B cells when pulsed with low concentrations of peptide, whereas CD40-B cells pulsed at saturating concentrations could only induce low-avidity CTL, which recognized peptide-pulsed target cells only. One high-avidity CTL line was subdoned and CTL dones, whose peptide concentration required for half-maximal lysis were less than 1 nM, could lyse cyclin-A2 expressing tumor cells. Taken together, cyclin A2 is an attractive candidate for immune intervention in a significant numher of cancer patients and high-avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells. (C) 2009 UICC.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1002/ijc.24629
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000271127400031&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-70349862891&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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