SEARCH:   Advanced

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 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 Citation Map 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. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The kinase insert domain-containing receptor is an angiogenesis-associated antigen recognized by human cytotoxic T lymphocytes Yuansheng Sun, Stefan Stevanovi, Mingxia Song, Astrid Schwantes, C. James Kirkpatrick, Dirk Schadendorf, and Klaus Cichutek From the Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen; Institute for Cell Biology, University of Tübingen, Tübingen; Skin Cancer Unit of German Cancer Research Center, Heidelberg; and Institute of Pathology, Johannes Gutenberg University, Mainz, Germany. Antigen-specific cancer immunotherapy directed toward tumor-nourishing angiogenic blood vessels holds the promise of high efficacy, low toxicity, and ease of application. To evaluate whether the human angiogenic kinase insert domain-containing receptor (KDR) can serve as a target for cellular immunotherapy, 19 peptide sequences with HLA-A*0201 motifs were selected by computer-based algorithms. Five peptides (KDR82-90, KDR288-297, KDR766-774, KDR1093-1101, KDR1035-1044) stimulated specific cytotoxic T lymphocytes (CTLs) from peripheral-blood mononuclear cells (PBMCs) of 3 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 important, KDR288-297 - specific CTLs lysed target cells transfected with HLA-A2/KDR cDNAs and a range of HLA-matched KDR+ angiogenic endothelial cells (aECs) and also recognized CD34+ endothelial progenitor cells. 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 up-regulated KDR and HLA class 1 expression. In Matrigel assays, recognition of aECs by specific CTLs triggered an antivascular 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]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020