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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 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 Citation Map 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. Articles by Byrd, J. C. Search for Related Content PubMed PubMed Citation Articles by Zhao, X. Articles by Byrd, J. C. Related Collections Free Research Articles Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical Xiaobin Zhao1,2, Rosa Lapalombella1, Trupti Joshi3, Carolyn Cheney1, Aruna Gowda1, Martha S. Hayden-Ledbetter6, Peter R. Baum6, Thomas S. Lin1, David Jarjoura5, Amy Lehman5, Donna Kussewitt4, Robert J. Lee2, Michael A. Caligiuri1,4, Susheela Tridandapani3, Natarajan Muthusamy1,4, and John C. Byrd1,2 1 Division of Hematology-Oncology, Department of Medicine, College of Medicine; 2 Division of Pharmaceutics, College of Pharmacy; 3 Division of Pulmonary Medicine, Department of Medicine, College of Medicine; 4 Department of Veterinary Biosciences; 5 Center for Biostatistics, the Ohio State University, Columbus; and 6 Trubion Pharmaceuticals, Seattle, WA 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 in the presence of a cross-linker, 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 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: 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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