論文

査読有り
2008年10月

Cyclin D1-Specific Cytotoxic T Lymphocytes Are Present in the Repertoire of Cancer Patients: Implications for Cancer Immunotherapy

CLINICAL CANCER RESEARCH
  • Eisei Kondo
  • ,
  • Britta Maecker
  • ,
  • Martin R. Weihrauch
  • ,
  • Claudia Wickenhauser
  • ,
  • WanYong Zeng
  • ,
  • Lee M. Nadler
  • ,
  • Joachim L. Schultze
  • ,
  • Michael S. von Bergwelt-Baildon

14
20
開始ページ
6574
終了ページ
6579
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1158/1078-0432.CCR-08-0825
出版者・発行元
AMER ASSOC CANCER RESEARCH

Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1 derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells.
Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay.
Results: After screening, at least two naturally processed and presented HLA-A*0201 - binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201 - matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer.
Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.1158/1078-0432.CCR-08-0825
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000260359600027&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-58149199123&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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