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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2275-2283. Prepublished online as a Blood First Edition Paper on November 12, 2008; DOI 10.1182/blood-2008-05-160747. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-05-160747v1 113/10/2275    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 Schliemann, C. Articles by Neri, D. Search for Related Content PubMed PubMed Citation Articles by Schliemann, C. Articles by Neri, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 30, 2008 Accepted October 30, 2008 Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2 Christoph Schliemann, Alessandro Palumbo, Kathrin Zuberbuhler, Alessandra Villa, Manuela Kaspar, Eveline Trachsel, Wolfram Klapper, Hans Dietrich Menssen, and Dario Neri* Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland Philochem AG, Zurich, Switzerland Department of Pathology, Haematopathology and Lymph Node Registry, University Hospital Schleswig-Holstein, Kiel, Germany Bayer Schering Pharma AG, Berlin, Germany * Corresponding author; email: neri{at}pharma.ethz.ch. The antibody-mediated delivery of therapeutic agents to sites of angiogenesis is an attractive strategy for anti-cancer therapy, but is largely unexplored in hematologic malignancies. In the present study, we show that the extra domain B (EDB) of fibronectin, a marker of angiogenesis, is expressed in B-cell non-Hodgkin lymphomas (NHLs), and that the human monoclonal anti-EDB antibody L19 can selectively localize to the lymphoma-associated sub-endothelial extracellular matrix. In vivo, the preferential accumulation of the antibody at the tumor site was confirmed by quantitative biodistribution analyses with radioiodinated antibody preparations. The fusion protein L19-IL2, which mediates the delivery of interleukin-2 (IL-2) to the neovasculature, displayed a superior anti-lymphoma activity compared to unconjugated IL-2 in localized and systemic xenograft models of NHL. When co-administered with rituximab, L19-IL2 induced complete remissions of established localized lymphomas and provided long-lasting protection from disseminated lymphoma. The combined use of rituximab and L19-IL2, which dramatically increases the infiltration of immune effector cells in lymphomas, may deserve clinical investigations, facilitated by the fact that L19-IL2 is currently being studied in phase II clinical trials in patients with solid tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: There will be blood: targeting tumor vasculature Nathan Fowler and Anas Younes Blood 2009 113: 2121-2122. [Full Text] [PDF] This article has been cited by other articles: N. Fowler and A. Younes There will be blood: targeting tumor vasculature Blood, March 5, 2009; 113(10): 2121 - 2122. [Full Text] [PDF]

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