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Blood, 1 August 2008, Vol. 112, No. 3, pp. 699-707. Prepublished online as a Blood First Edition Paper on June 2, 2008; DOI 10.1182/blood-2007-11-122465. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-122465v1 112/3/699    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 Lin, W. Articles by Strome, S. E. Search for Related Content PubMed PubMed Citation Articles by Lin, W. Articles by Strome, S. E. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Fc-dependent expression of CD137 on human NK cells: insights into "agonistic" effects of anti-CD137 monoclonal antibodies Wei Lin1,*, Caroline J. Voskens2,*, Xiaoyu Zhang1, Daniel G. Schindler3, Aaron Wood1, Erin Burch1, Yadong Wei4, Lieping Chen5, Guoliang Tian6, Koji Tamada1, Lai-Xi Wang4, Dan H. Schulze1,7, Dean Mann2, and Scott E. Strome1,7 1 Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore; 2 Department of Pathology, University of Maryland School of Medicine, Baltimore; 3 GTC Biotherapeutics, Framingham, MA; 4 Institute of Human Virology, University of Maryland, Baltimore; 5 Department of Dermatology, Johns Hopkins University, Baltimore, MD; 6 Division of Biostatistics, University of Maryland Greenebaum Cancer Center, Baltimore; and 7 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore CD137 (4-1BB) is a costimulatory mol-ecule that can be manipulated for the treatment of cancer and autoimmune disease. Although it is known that agonistic antibodies (mAbs) against CD137 enhance the rejection of murine tumors in a natural killer (NK) cell– and T cell–dependent fashion, the mechanism for NK dependence is poorly understood. In this study, we evaluated the ability of 2 different glycoforms of a chimerized antihuman CD137 mAb, an aglycosylated (GA) and a low fucose form (GG), to react with human NK cells. Both mAbs bound similarly to CD137 and partially blocked the interaction between CD137 and CD137 ligand. However, unlike GA mAb, immobilized GG mAb activated NK cells and enhanced CD137 expression. These effects were seemingly dependent on Fc interaction with putative Fc receptors on the NK-cell surface, as only the immobilized Fc-fragment of GG was required for CD137 expression. Furthermore, CD137 expression could be enhanced with antibodies directed against non-CD137 epitopes, and the expression levels directly correlated with patterns of Fc-glycosylation recognized to improve Fc interaction with Fc receptors. Our data suggest that CD137 can be enhanced on NK cells in an Fc-dependent fashion and that expression correlates with phenotypic and functional parameters of activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Vickers The doctor's dilemma: stimulating T cells Blood, October 15, 2009; 114(16): 3361 - 3362. [Full Text] [PDF] T. Baessler, C. Buechele, M. Krusch, B. J Schmiedel, L. Kanz, and H. R Salih The Role of CD137 and Its Ligand in Chronic Lymphocytic Leukemia (CLL) Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3130 - 3130. [Abstract]

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