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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4903-4913. Prepublished online as a Blood First Edition Paper on January 5, 2009; DOI 10.1182/blood-2008-11-187401. This Article Full Text (PDF) All Versions of this Article: blood-2008-11-187401v1 113/20/4903    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 Pagel, J. M. Articles by Press, O. W. Search for Related Content PubMed PubMed Citation Articles by Pagel, J. M. Articles by Press, O. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 3, 2008 Accepted December 11, 2008 A comparative analysis of conventional and pretargeted radioimmunotherapy of B-cell lymphomas by targeting CD20, CD22, and HLA-DR singly and in combinations John M. Pagel*, Nural Orgun, Donald K. Hamlin, D. Scott Wilbur, Theodore A. Gooley, Ajay K. Gopal, Steven I. Park, Damian J. Green, Yukang Lin, and Oliver W. Press Fred Hutchinson Cancer Research Center, Seattle, WA, United States Department of Radiation Oncology, University of Washington, Seattle, WA, United States Department of Medicine, University of Washington, Seattle, WA, United States * Corresponding author; email: jpagel{at}fhcrc.org. Relapsed B cell lymphomas are currently incurable with conventional chemotherapy and radiation treatments. Radiolabeled antibodies directed against B cell surface antigens have emerged as effective and safe therapies for relapsed lymphomas. We therefore investigated the potential utility of both directly radiolabeled 1F5 (anti-CD20), HD39 (anti-CD22), and Lym-1 (anti-DR) antibodies (Ab) and of pretargeted radioimmunotherapy (RIT) using Ab-streptavidin (SA) conjugates, followed by an N-acetylgalactosamine dendrimeric clearing agent and radiometal-labeled DOTA-biotin, for treatment of lymphomas in mouse models using Ramos, Raji, and FL-18 human lymphoma xenografts. This study demonstrates the marked superiority of pretargeted RIT for each of the antigenic targets with more complete tumor regressions and longer mouse survival compared to conventional one-step RIT. The Ab-SA conjugate yielding the best tumor regression and progression-free survival after pretargeted RIT varied depending upon the lymphoma cell line employed, with 1F5 Ab-SA and Lym-1 Ab-SA conjugates yielding the most promising results overall. Contrary to expectations, the best rates of mouse survival were obtained using optimal single Ab-SA conjugates rather than combinations of conjugates targeting different antigens. We hypothesize that clinical implementation of pretargeted RIT methods will provide a meaningful prolongation of survival for patients with relapsed lymphomas compared with currently available treatment strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Some like it hot: lymphoma radioimmunotherapy David M. Goldenberg Blood 2009 113: 4823-4824. [Full Text] [PDF] This article has been cited by other articles: D. M. Goldenberg Some like it hot: lymphoma radioimmunotherapy Blood, May 14, 2009; 113(20): 4823 - 4824. [Full Text] [PDF]

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