SEARCH:   Advanced

Blood, 3 September 2009, Vol. 114, No. 10, pp. 2131-2139. Prepublished online as a Blood First Edition Paper on July 8, 2009; DOI 10.1182/blood-2009-03-209387. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-03-209387v1 114/10/2131    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 CrossRef Google Scholar Articles by Wilde, S. Articles by Schendel, D. J. PubMed PubMed Citation Articles by Wilde, S. Articles by Schendel, D. J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity Susanne Wilde1, Daniel Sommermeyer2, Bernhard Frankenberger1, Matthias Schiemann3,4, Slavoljub Milosevic1, Stefani Spranger1, Heike Pohla4,5, Wolfgang Uckert2,6, Dirk H. Busch3,4,7, and Dolores J. Schendel1,4 1 Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich; 2 Max-Delbrueck-Center for Molecular Medicine, Berlin; 3 Institute of Medical Microbiology, Immunology, and Hygiene, Technical University Munich, Munich; 4 Clinical Cooperation Group "Immune Monitoring," Helmholtz Zentrum München, German Research Center for Environmental Health, Munich; 5 Laboratory of Tumor Immunology, LIFE-Center, Ludwig-Maximilians-University, Munich; 6 Humboldt University Berlin, Institute of Biology, Berlin; and 7 Clinical Cooperation Group Antigen-Specific Immunotherapy, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany Adoptive transfer of T cells expressing transgenic T-cell receptors (TCRs) with antitumor function is a hopeful new therapy for patients with advanced tumors; however, there is a critical bottleneck in identifying high-affinity TCR specificities needed to treat different malignancies. We have developed a strategy using autologous dendritic cells cotransfected with RNA encoding an allogeneic major histocompatibility complex molecule and a tumor-associated antigen to obtain allo-restricted peptide-specific T cells having superior capacity to recognize tumor cells and higher functional avidity. This approach provides maximum flexibility because any major histocompatibility complex molecule and any tumor-associated antigen can be combined in the dendritic cells used for priming of autologous T cells. TCRs of allo-restricted T cells, when expressed as transgenes in activated peripheral blood lymphocytes, transferred superior function compared with self-restricted TCR. This approach allows high-avidity T cells and TCR specific for tumor-associated self-peptides to be easily obtained for direct adoptive T-cell therapy or for isolation of therapeutic transgenic TCR sequences. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020