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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-02-0378. This Article Full Text (PDF) All Versions of this Article: 2002-02-0378v1 101/6/2184    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bello-Fernandez, C. Articles by Knapp, W. Search for Related Content PubMed PubMed Citation Articles by Bello-Fernandez, C. Articles by Knapp, W. Social Bookmarking                   What's this? Submitted February 5, 2002 Accepted October 29, 2002 Retrovirus-mediated IL-7 expression in leukemic dendritic cells generated from primary acute myelogenous leukemias enhances their functional properties Concha Bello-Fernandez*, Jana Stasakova, Alexander Renner, Nicole Carballido-Perrig, Margit Koening, Martina Waclavicek, Otto Madjic, Leopold Oehler, Oskar Haas, Jose M Carballido, Michael Buschle, and Walter Knapp Institute of Immunology, Vienna International Research Cooperation Center (VIRCC) at Novartis, Vienna, Austria Novartis Forschungsinstitut, Vienna, Austria CCRI St. Anna Childrens Hospital, Vienna, Austria Division of Hematology, Internal Medicine I, University of Vienna, Vienna, Austria Intercell AG, Vienna, Austria * Corresponding author; email: concha.bello{at}univie.ac.at. Myeloid lineage-derived dendritic cells (DCs) are considered the professional antigen-presenting cell type responsible for eliciting T-cell-mediated immune responses. Acute myelogenous leukemia (AML) is a disease where tumor antigens are expressed by the malignant clone that also has the potential to differentiate into DC-like cells (leukemic-DCs) with antigen-presenting capacity. This study investigated whether the constitutive expression of the interleukin-7 (IL-7) cytokine into primary AML cells during their differentiation towards DCs-type results in superior antigen presenting cells. A bicistronic retroviral vector encoding the IL-7 cytokine and the surface immunoselectable low nerve growth factor receptor (LNGFr) gene was constructed and employed for transduction experiments. A serum-free system was used to transduce and differentiate leukemic cells towards leukemic-DCs. Eight AML patients were included in the study. The transduction efficiency with the cytokine vector varied between patients ranging from 5% to 30% as judged by LNGFr expression. The leukemic origin of the transduced cells was confirmed in a patient with a chromosomal translocation t(9:11), by fluorescence in situ hybridisation analysis (FISH). Cytokine modified-cells consistently secrete IL-7(mean415pg±190/106cells/48h, n=5). We demonstrate that IL-7 transduced cells are included in the differentiated leukemic-DC subset, and, as shown in a particular case, that about half of the mature CD80+ and CD83+ populations co-express the LNGFr transgene. In addition, IL-7 modified-leukemic cells induce stronger allo-T cell stimulation and higher amounts of IL-2 production in T cells compared to control groups. Finally, cytokine transduced leukemic-DCs can effectively prime and generate cytotoxic T lymphocytes (CTL) against autologous leukemic blasts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Cignetti, A. Vallario, I. Roato, P. Circosta, B. Allione, L. Casorzo, P. Ghia, and F. Caligaris-Cappio Leukemia-Derived Immature Dendritic Cells Differentiate into Functionally Competent Mature Dendritic Cells That Efficiently Stimulate T Cell Responses J. Immunol., August 15, 2004; 173(4): 2855 - 2865. [Abstract] [Full Text] [PDF]

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