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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2931-2939. Prepublished online as a Blood First Edition Paper on July 12, 2007; DOI 10.1182/blood-2006-11-058750. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-11-058750v1 110/8/2931    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 Citing Articles via Google Scholar Google Scholar Articles by Schuster, I. G. Articles by Krackhardt, A. M. Search for Related Content PubMed PubMed Citation Articles by Schuster, I. G. Articles by Krackhardt, A. M. Related Collections Immunotherapy Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies Ingrid G. Schuster1, Dirk H. Busch2, Elfriede Eppinger1, Elisabeth Kremmer1, Slavoljub Milosevic1, Christine Hennard1, Christina Kuttler3, Joachim W. Ellwart1, Bernhard Frankenberger1, Elfriede Nößner1, Christoph Salat4, Christian Bogner5, Arndt Borkhardt6, Hans-Jochem Kolb7, and Angela M. Krackhardt1 1 Institute of Molecular Immunology, Forschungszeutrum für Umwelt und Gesundheit (GSF)–National Research Center for Environment and Health, Munich; 2 Clinical Cooperation Group Immunmonitoring, GSF–National Research Center for Environment and Health and Institute of Microbiology, Technische Universität, Munich; 3 Institute of Biomathematics and Biometry, GSF–National Research Center for Environment and Health, Neuherberg; 4 Hämato-Onkologische Schwerpunkt-Praxis, Munich; 5 Medizinische Klinik III, Innere Medizin mit Schwerpunkt Hämatologie und Onkologie, Technische Universität, Munich; 6 Klinik für Kinder-Onkologie, -Hämatologie und -Immunologie, Heinrich-Heine-Universität, Düsseldorf; and 7 Clinical Cooperation Group Hämatopoetische Zelltransplantation, GSF–National Research Center for Environment and Health and Medizinische Klinik III mit Schwerpunkt Hämatologie und Onkologie, Ludwig-Maximilians-Universität, Munich, Germany Cell-based immunotherapy in settings of allogeneic stem cell transplantation or donor leukocyte infusion has curative potential, especially in hematologic malignancies. However, this approach is severely restricted due to graft-versus-host disease (GvHD). This limitation may be overcome if target antigens are molecularly defined and effector cells are specifically selected. We chose formin-related protein in leukocytes 1 (FMNL1) as a target antigen after intensive investigation of its expression profile at the mRNA and protein levels. Here, we confirm restricted expression in peripheral blood mononuclear cells (PBMCs) from healthy donors but also observe overexpression in different leukemias and aberrant expression in transformed cell lines derived from solid tumors. We isolated allorestricted T-cell clones expressing a single defined TCR recognizing a particular HLA-A2–presented peptide derived from FMNL1. This T-cell clone showed potent antitumor activity against lymphoma and renal cell carcinoma cell lines, Epstein-Barr virus (EBV)–transformed B cells, and primary tumor samples derived from patients with chronic lymphocytic leukemia (CLL), whereas nontransformed cells with the exception of activated B cells were only marginally recognized. Allorestricted TCRs with specificity for naturally presented FMNL1-derived epitopes may represent promising reagents for the development of adoptive therapies in lymphoma and other malignant diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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