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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3434-3440. Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-05-021675. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021675v1 108/10/3434    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 Kashkar, H. Articles by Krönke, M. Search for Related Content PubMed PubMed Citation Articles by Kashkar, H. Articles by Krönke, M. Related Collections Immunobiology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY XIAP targeting sensitizes Hodgkin lymphoma cells for cytolytic T-cell attack Hamid Kashkar, Jens-Michael Seeger, Andreas Hombach, Anke Deggerich, Benjamin Yazdanpanah, Olaf Utermöhlen, Gerd Heimlich, Hinrich Abken, and Martin Krönke From the Institute for Medical Microbiology, Immunology and Hygiene, Center for Molecular Medicine Cologne (CMMC), Germany; Tumorgenetics, Clinic I Internal Medicine, University of Cologne, Germany; and the Laboratory of Signal Transduction, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Research Triangle Park, NC. The immunosurveillance of Hodgkin lymphoma (HL) by cytotoxic T lymphocytes (CTLs) is insufficient, and the clinical experience with adoptive transfer of CTLs is limited. We have previously reported that defects in mitochondrial apoptotic pathways and elevated XIAP expression confer resistance to different apoptotic stimuli in HL cells. Here, we aimed to develop molecular strategies to overcome the resistance of HL cells against CTL-mediated killing via granzyme B (grzB). In HL cells, grzB-induced mitochondrial release of proapoptotic Smac is blocked, which results in complete abrogation of cytotoxicity mediated by CTLs. Cytosolic expression of recombinant mature Smac enhanced caspase activity induced by grzB and restored the apoptotic response of HL cells. Similarly, down-regulation of XIAP by RNA interference markedly enhanced the susceptibility of HL cells for CTL-mediated cytotoxicity. XIAP gene knockdown sensitized HL cells for killing by antigen-specific CTLs redirected by grafting with a chimeric anti-CD30scFv-CD3zeta immunoreceptor. The results suggest that XIAP targeting by Smac agonists or XIAP-siRNA can be used as a synergistic strategy for cellular immunotherapy of Hodgkin lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. P. Kater, M. H. J. van Oers, and T. J. Kipps Cellular immune therapy for chronic lymphocytic leukemia Blood, October 15, 2007; 110(8): 2811 - 2818. [Abstract] [Full Text] [PDF] H. Kashkar, A. Deggerich, J.-M. Seeger, B. Yazdanpanah, K. Wiegmann, D. Haubert, C. Pongratz, and M. Kronke NF-{kappa}B-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs Blood, May 1, 2007; 109(9): 3982 - 3988. [Abstract] [Full Text] [PDF]

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