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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2569-2577. Prepublished online as a Blood First Edition Paper on April 17, 2007; DOI 10.1182/blood-2006-12-062927. This Article Full Text (PDF) All Versions of this Article: blood-2006-12-062927v1 110/7/2569    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 Zhao, X. B Articles by Byrd, J. C. Search for Related Content PubMed PubMed Citation Articles by Zhao, X. B Articles by Byrd, J. C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 13, 2006 Accepted February 21, 2007 Targeting CD37+ lymphoid malignancies with a novel engineered small modular immunopharmaceutical Xiaobin B Zhao, Rosa Lapalombella, Trupti Joshi, Carolyn Cheney, Aruna Gowda, Martha S Hayden-Ledbetter, Peter R Baum, Thomas S Lin, David Jarjoura, Amy Lehman, Donna Kussewitt, Robert J Lee, Michael A Caligiuri, Susheela Tridandapani, Natarajan Muthusamy, and John C. Byrd* Dept of Medicine, Division of Hematology-Oncology, Ohio State University, Columbus, OH Dept of Medicine, Division of Pulmonary Medicine, Ohio State University, Columbus, OH Trubion Pharmaceuticals, Seatle, WA Center for Biostatistics, Ohio State University, Columbus, OH Dept of Veterinary Biosciences, Ohio State University, Columbus, OH Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH * Corresponding author; email: john.byrd{at}osumc.edu. CD37 is a lineage-specific B-cell antigen that to date has been neglected as an attractive therapeutic target. To exploit this, novel CD37-specific small modular immunopharmaceuticals (CD37-SMIP) that include variable regions linked to modified human IgG1 hinge, CH2 and CH3 domains were designed. The lead CD37-SMIP molecule induces potent apoptosis and antibody dependent cellular cytotoxicity against B-cell leukemia/lymphoma cell lines and primary chronic lymphocytic leukemia (CLL) cells superior to therapeutic antibodies used in these diseases. The CD37-SMIP dependent ADCC function in vitro was mediated by natural killer (NK) cells but not naive or activated monocytes. Significant in vivo therapeutic efficacy was demonstrated in a SCID mouse xenograft leukemia/lymphoma model. Depletion of NK cells in this mouse model resulted in diminished efficacy further supported the in vivo importance of NK cells in SMIP therapy. These findings provide strong justification for CD37 as a therapeutic target and introduce small novel small modular immunopharmaceuticals as a novel class of targeted therapies for B-cell malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Immunotherapy of B-cell malignancies: first MABs, now SMIPs Richard R. Furman and John P. Leonard Blood 2007 110: 2218. [Full Text] [PDF] This article has been cited by other articles: B. D. Cheson and J. P. Leonard Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma N. Engl. J. Med., August 7, 2008; 359(6): 613 - 626. [Full Text] [PDF] S. O'Brien New Agents in the Treatment of CLL Hematology, January 1, 2008; 2008(1): 457 - 464. [Abstract] [Full Text] [PDF] J. M. Roda and J. C. Byrd Fc{gamma}RIIIa role in rituximab efficacy Blood, October 1, 2007; 110(7): 2220 - 2220. [Full Text] [PDF]

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