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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1476-1483. Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-05-1912. This Article Full Text (PDF) All Versions of this Article: 2005-05-1912v1 107/4/1476    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sun, Y. Articles by Cichutek, K. Search for Related Content PubMed PubMed Citation Articles by Sun, Y. Articles by Cichutek, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 11, 2005 Accepted October 4, 2005 The kinase insert domain-containing receptor is an angiogenesis-associated antigen recognized by human cytotoxic T lymphocytes Yuansheng Sun*, Stefan Stevanovic, Mingxia Song, Astrid Schwantes, C J Kirkpatrick, Dirk Schadendorf, and Klaus Cichutek Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany Institute for Cell Biology, University of Tuebingen, Tuebingen, Germany Skin Cancer Unit, German Cancer Research Center, Heidelberg, Germany Institute of Pathology, Johannes Gutenberg University, Mainz, Germany * Corresponding author; email: sunyu{at}pei.de. Antigen-specific cancer immunotherapy directed towards tumor-nourishing angiogenic blood vessels holds the promise of high efficacy, low toxicity and ease of application. To evaluate if the human angiogenic kinase insert domain-containing receptor (KDR) can serve as a target for cellular immunotherapy, nineteen peptide sequences with HLA-A*0201 motifs were selected by computer-based algorithms. Five peptides (KDR82-90, KDR288-297, KDR766-774, KDR1093-1101, or KDR1035-1044) stimulated specific cytotoxic T lymphocytes (CTLs) from PBMCs of three HLA-A*0201 donors. The decapeptide KDR288-297 was efficient in sensitizing target cells for recognition by a CTL clone at a concentration of 10 nM. More importantly, KDR288-297-specific CTLs lyzed target cells transfected with HLA-A2/KDR cDNAs and a range of HLA-matched KDR+ angiogenic endothelial cells (aECs) and recognized CD34+ endothelial progenitor cells as well. The specificity of CTLs was further confirmed by tetramer assay and cold-target inhibition assay. In addition, ex vivo exposure of aECs to the inflammatory cytokines enhanced CTL reactivity, which is in keeping with upregulated KDR and HLA class I expression. In Matrigel assays, recognition of aECs by specific CTLs triggered an anti-vascular effect. These findings provide the first proof of the antigenic property of KDR protein, and may be useful for devising new immunotherapeutic approaches to human cancers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Sun, M. Song, E. Jager, C. Schwer, S. Stevanovic, S. Flindt, J. Karbach, X. D. Nguyen, D. Schadendorf, and K. Cichutek Human CD4+ T Lymphocytes Recognize a Vascular Endothelial Growth Factor Receptor-2-Derived Epitope in Association with HLA-DR Clin. Cancer Res., July 1, 2008; 14(13): 4306 - 4315. [Abstract] [Full Text] [PDF] A. M. Asemissen, U. Keilholz, S. Tenzer, M. Muller, S. Walter, S. Stevanovic, H. Schild, A. Letsch, E. Thiel, H.-G. Rammensee, et al. Identification of a Highly Immunogenic HLA-A*01-Binding T Cell Epitope of WT1 Clin. Cancer Res., December 15, 2006; 12(24): 7476 - 7482. [Abstract] [Full Text] [PDF]

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