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Blood, 1 January 2007, Vol. 109, No. 1, pp. 365-373. Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-04-014100. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-014100v1 109/1/365    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 Wehler, T. C. Articles by Herr, W. Search for Related Content PubMed PubMed Citation Articles by Wehler, T. C. Articles by Herr, W. Related Collections Immunobiology Neoplasia Transplantation Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines Thomas C. Wehler1, Marion Nonn1, Britta Brandt1, Cedrik M. Britten1, Mark Gröne1, Mariya Todorova1, Irina Link1, Shamsul A. Khan1, Ralf G. Meyer1, Christoph Huber1, Udo F. Hartwig1,, and Wolfgang Herr1, 1 Department of Medicine III, Hematology, and Oncology, Johannes Gutenberg-University of Mainz, Mainz, Germany In HLA-incompatible hematopoietic stem cell transplantation, alloreactive donor T cells recognizing recipient mismatch HLA cause severe graft-versus-host disease (GVHD). Strategies allowing the selective depletion of alloreactive T cells as well as the enhancement of graft-versus-malignancy immunity would be beneficial. We generated donor CD8 T-cell lines in vitro using allogeneic recipient cells mismatched at a single HLA class I allele or haplotype as stimulators. Recipient cells were obtained from acute myeloid leukemias, renal-cell carcinomas, and CD40L-induced B lymphoblasts. Resulting alloreactive T cells were activated by incubating day 21 T-cell cultures with HLA-mismatch transfected K562 cells or recipient-derived fibroblasts. Selective allodepletion (SAD) was subsequently performed by a newly developed immunomagnetic depletion approach targeting the tumor necrosis factor receptor molecule CD137 (4-1BB). Compared with other activation-induced antigens, CD137 showed a superior performance based on a consistently low baseline expression and a rapid up-regulation following alloantigen stimulation. In 15 different SAD experiments, the frequency of alloreactive CD8 T cells was reduced to a median of 9.5% compared with undepleted control populations. The allodepleted T-cell subsets maintained significant antitumor and antiviral CD8 responses. In vitro expansion of tumor-reactive T cells followed by CD137-mediated SAD might enhance the antitumor efficacy of T-cell allografts with lower risk of inducing GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation Persis J. Amrolia, Giada Muccioli-Casadei, Helen Huls, Stuart Adams, April Durett, Adrian Gee, Eric Yvon, Heidi Weiss, Mark Cobbold, H. Bobby Gaspar, Cliona Rooney, Ingrid Kuehnle, Victor Ghetie, John Schindler, Robert Krance, Helen E. Heslop, Paul Veys, Ellen Vitetta, and Malcolm K. Brenner Blood 2006 108: 1797-1808. [Abstract] [Full Text] [PDF] This article has been cited by other articles: C. Stuehler, S. Mielke, M. Chatterjee, J. Duell, S. Lurati, F. Rueckert, H. Einsele, R. C. Bargou, and M. S. Topp Selective depletion of alloreactive T cells by targeted therapy of heat shock protein 90: a novel strategy for control of graft-versus-host disease Blood, September 24, 2009; 114(13): 2829 - 2836. [Abstract] [Full Text] [PDF] O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF] S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al. A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique Blood, April 15, 2008; 111(8): 4392 - 4402. [Abstract] [Full Text] [PDF] S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al. Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease Blood, September 1, 2007; 110(5): 1689 - 1697. [Abstract] [Full Text] [PDF] M. Wolfl, J. Kuball, W. Y. Ho, H. Nguyen, T. J. Manley, M. Bleakley, and P. D. Greenberg Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities Blood, July 1, 2007; 110(1): 201 - 210. 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