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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 28, 2006 Accepted July 9, 2007 Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematological and other malignancies Ingrid G Schuster, Dirk H Busch, Elfriede Eppinger, Elisabeth Kremmer, Slavoljub Milosevic, Christine Hennard, Christina Kuttler, Joachim W Ellwart, Bernhard Frankenberger, Elfriede Noessner, Christoph Salat, Christian Bogner, Arndt Borkhardt, Hans-Jochem Kolb, and Angela M Krackhardt* Institute of Molecular Immunology, GSF - National Research Center for Environment and Health, Munich, Germany Clinical Cooperation Group Immunmonitoring, GSF National Research Center for Environment & Health, & Institute of Microbiology, Technische Univ., Munich, Germany Institute of Biomathematics and Biometry, GSF - National Research Center for Environment and Health, Neuherberg, Germany Hamato-Onkologische Schwerpunkt-Praxis, Munich, Germany Medizinische Klinik III, Innere Medizin mit Schwerpunkt Hematologie und Onkologie, Technische Universitat, Munich, Germany Klinik fur Kinder-Onkologie, -Hamatologie und -Immunologie, Heinrich-Heine-Universitat, Düsseldorf, Germany Clinical Cooperation Group Hematopoietic cell transplan., GSF National Research Center for Environment & Health, & Ludwig-Maximilians-Universitat, Munich, Germany * Corresponding author; email: angela.krackhardt{at}gsf.de. Cell-based immunotherapy in settings of allogeneic stem cell transplantation or donor leukocyte infusion has curative potential, especially in hematological 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 PBMC 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 non-transformed 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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