SEARCH:   Advanced

Blood, 15 November 2007, Vol. 110, No. 10, pp. 3564-3572. Prepublished online as a Blood First Edition Paper on July 27, 2007; DOI 10.1182/blood-2007-02-075010. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-02-075010v1 110/10/3564    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 Jorritsma, A. Articles by Haanen, J. B. A. G. Search for Related Content PubMed PubMed Citation Articles by Jorritsma, A. Articles by Haanen, J. B. A. G. Related Collections Neoplasia Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Selecting highly affine and well-expressed TCRs for gene therapy of melanoma Annelies Jorritsma1, Raquel Gomez-Eerland1, Maarten Dokter1, Willeke van de Kasteele1, Yvonne M. Zoet2, Ilias I. N. Doxiadis2, Nathalie Rufer3, Pedro Romero3, Richard A. Morgan4, Ton N. M. Schumacher1, and John B. A. G. Haanen1 1 Department of Immunology, the Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands; 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands; 3 Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland; and 4 Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD A recent phase 1 trial has demonstrated that the generation of tumor-reactive T lymphocytes by transfer of specific T-cell receptor (TCR) genes into autologous lymphocytes is feasible. However, compared with results obtained by infusion of tumor-infiltrating lymphocytes, the response rate observed in this first TCR gene therapy trial is low. One strategy that is likely to enhance the success rate of TCR gene therapy is the use of tumor-reactive TCRs with a higher capacity for tumor cell recognition. We therefore sought to develop standardized procedures for the selection of well-expressed, high-affinity, and safe human TCRs. Here we show that TCR surface expression can be improved by modification of TCR alpha and beta sequences and that such improvement has a marked effect on the in vivo function of TCR gene-modified T cells. From a panel of human, melanoma-reactive TCRs we subsequently selected the TCR with the highest affinity. Furthermore, a generally applicable assay was used to assess the lack of alloreactivity of this TCR against a large series of common human leukocyte antigen alleles. The procedures described in this study should be of general value for the selection of well- and stably expressed, high-affinity, and safe human TCRs for subsequent clinical testing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020