SEARCH:   Advanced

Blood, 15 November 2003, Vol. 102, No. 10, pp. 3530-3540. Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-05-1524. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1524v1 102/10/3530    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 Heemskerk, M. H. M. Articles by Falkenburg, J. H. F. Search for Related Content PubMed PubMed Citation Articles by Heemskerk, M. H. M. Articles by Falkenburg, J. H. F. Related Collections Immunobiology Neoplasia Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region Mirjam H. M. Heemskerk, Manja Hoogeboom, Roelof A. de Paus, Michel G. D. Kester, Menno A. W. G. van der Hoorn, Els Goulmy, Roel Willemze, and J. H. Frederik Falkenburg From the Department of Hematology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands. Donor-derived T lymphocytes directed against minor histocompatibility antigens (mHags) exclusively expressed on cells of the hematopoietic lineages can eliminate hematologic malignancies. Transfer of T-cell receptors (TCRs) directed against these mHags into T lymphocytes may provide a strategy to generate antileukemic T cells. To investigate the feasibility of this strategy the TCR usage of mHag HA-2-specific T-cell clones was characterized. Thirteen different types of HA-2-specific T-cell clones were detected, expressing TCRs with diversity in TCR - and -chain usage, however, containing in the TCR chain a single conserved gene segment J42, indicating that J42 is involved in HA-2-specific recognition. We transferred various HA-2 TCRs into T lymphocytes from HLA-A2-positive HA-2-negative individuals resulting in T cells with redirected cytolytic activity against HA-2-expressing target cells. Transfer of chimeric TCRs demonstrated that the HA-2 specificity is not only determined by the J42 region but also by the N-region of the chain and the CDR3 region of the chain. Finally, when HA-2 TCRs were transferred into T cells from HLA-A2-negative donors, the HA-2 TCR-modified T cells exerted potent antileukemic reactivity without signs of anti-HLA-A2 alloreactivity. These results indicate that HA-2 TCR transfer may be used as an alternative strategy to generate HA-2-specific T cells to treat hematologic malignancies of HLA-A2-positive, HA-2-expressing patients that received transplants from HLA-A2-matched or -mismatched donors. (Blood. 2003;102:3530-3540) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. L. J. van der Heiden, R. de Boer, D. M. van der Steen, M. G. D. Kester, M. W. A. G. van der Hoorn, W. M. E. Haarman, H. E. Barnby-Porritt, J. W. Fry, C. E. Napper, E. W. A. Marijt, et al. Identification of Varicella-Zoster Virus-Specific CD8 T Cells in Patients after T-Cell-Depleted Allogeneic Stem Cell Transplantation J. Virol., July 15, 2009; 83(14): 7361 - 7364. [Abstract] [Full Text] [PDF] M. M. van Loenen, R. S. Hagedoorn, M. G.D. Kester, M. Hoogeboom, R. Willemze, J.H. F. Falkenburg, and M. H.M. Heemskerk Kinetic Preservation of Dual Specificity of Coprogrammed Minor Histocompatibility Antigen-Reactive Virus-Specific T Cells Cancer Res., March 1, 2009; 69(5): 2034 - 2041. [Abstract] [Full Text] [PDF] L. T. van der Veken, M. Diez Campelo, M. A. W. G. van der Hoorn, R. S. Hagedoorn, H. M. E. van Egmond, J. van Bergen, R. Willemze, J. H. F. Falkenburg, and M. H. M. Heemskerk Functional Analysis of Killer Ig-Like Receptor-Expressing Cytomegalovirus-Specific CD8+ T Cells J. Immunol., January 1, 2009; 182(1): 92 - 101. [Abstract] [Full Text] [PDF] M. Griffioen, H.M. E. van Egmond, H. Barnby-Porritt, M. A.W.G. van der Hoorn, R. S. Hagedoorn, M. G.D. Kester, N. Schwabe, R. Willemze, J.H. F. Falkenburg, and M. H.M. Heemskerk Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application Haematologica, October 1, 2008; 93(10): 1535 - 1543. [Abstract] [Full Text] [PDF] E. Kieback, J. Charo, D. Sommermeyer, T. Blankenstein, and W. Uckert A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer PNAS, January 15, 2008; 105(2): 623 - 628. [Abstract] [Full Text] [PDF] S. Thomas, S.-A. Xue, M. Cesco-Gaspere, E. San Jose, D. P. Hart, V. Wong, R. Debets, B. Alarcon, E. Morris, and H. J. Stauss Targeting the Wilms Tumor Antigen 1 by TCR Gene Transfer: TCR Variants Improve Tetramer Binding but Not the Function of Gene Modified Human T Cells J. Immunol., November 1, 2007; 179(9): 5803 - 5810. [Abstract] [Full Text] [PDF] A. U. van Lent, M. Nagasawa, M. M. van Loenen, R. Schotte, T. N. M. Schumacher, M. H. M. Heemskerk, H. Spits, and N. Legrand Functional Human Antigen-Specific T Cells Produced In Vitro Using Retroviral T Cell Receptor Transfer into Hematopoietic Progenitors J. Immunol., October 15, 2007; 179(8): 4959 - 4968. [Abstract] [Full Text] [PDF] M. H. M. Heemskerk, R. S. Hagedoorn, M. A. W. G. van der Hoorn, L. T. van der Veken, M. Hoogeboom, M. G. D. Kester, R. Willemze, and J. H. F. Falkenburg Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex Blood, January 1, 2007; 109(1): 235 - 243. [Abstract] [Full Text] [PDF] L. T. van der Veken, R. S. Hagedoorn, M. M. van Loenen, R. Willemze, J.H. F. Falkenburg, and M. H.M. Heemskerk {alpha}{beta} T-Cell Receptor Engineered {gamma}{delta} T Cells Mediate Effective Antileukemic Reactivity. Cancer Res., March 15, 2006; 66(6): 3331 - 3337. [Abstract] [Full Text] [PDF] F. M. Kloosterboer, S. A. P. van Luxemburg-Heijs, R. A. van Soest, H. M. E. van Egmond, R. Willemze, and J. H. F. Falkenburg Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor histocompatibility antigens in response to inflammatory cytokines: relevance for allogeneic immunotherapy of leukemia Blood, December 1, 2005; 106(12): 3955 - 3957. [Abstract] [Full Text] [PDF] S.-A. Xue, L. Gao, D. Hart, R. Gillmore, W. Qasim, A. Thrasher, J. Apperley, B. Engels, W. Uckert, E. Morris, et al. Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene-transduced human T cells Blood, November 1, 2005; 106(9): 3062 - 3067. [Abstract] [Full Text] [PDF] C. Lotz, S. A. Mutallib, N. Oehlrich, U. Liewer, E. A. Ferreira, M. Moos, M. Hundemer, S. Schneider, S. Strand, C. Huber, et al. Targeting Positive Regulatory Domain I-Binding Factor 1 and X Box-Binding Protein 1 Transcription Factors by Multiple Myeloma-Reactive CTL J. Immunol., July 15, 2005; 175(2): 1301 - 1309. [Abstract] [Full Text] [PDF] E. C. Morris, A. Tsallios, G. M. Bendle, S.-a. Xue, and H. J. Stauss A critical role of T cell antigen receptor-transduced MHC class I-restricted helper T cells in tumor protection PNAS, May 31, 2005; 102(22): 7934 - 7939. [Abstract] [Full Text] [PDF] J. van Bergen, A. Thompson, A. van der Slik, T. H. M. Ottenhoff, J. Gussekloo, and F. Koning Phenotypic and Functional Characterization of CD4 T Cells Expressing Killer Ig-Like Receptors J. Immunol., December 1, 2004; 173(11): 6719 - 6726. [Abstract] [Full Text] [PDF] J. Rice, S. Buchan, H. Dewchand, E. Simpson, and F. K. Stevenson DNA Fusion Vaccines Induce Targeted Epitope-Specific CTLs against Minor Histocompatibility Antigens from a Normal or Tolerized Repertoire J. Immunol., October 1, 2004; 173(7): 4492 - 4499. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020