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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 6, 2007 Accepted May 12, 2008 Fc dependent expression of CD137 on human NK cells: insights into "agonistic" effects of anti-CD137 monoclonal antibodies Wei Lin, Caroline J Voskens, Xiaoyu Zhang, Daniel G Schindler, Aaron Wood, Erin Burch, Yadong Wei, Lieping Chen, Guoliang Tian, Koji Tamada, Lai-Xi Wang, Dan H Schulze, Dean Mann, and Scott E Strome* Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, MD, United States Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States GTC Biotherapeutic Inc, GTC Biotherapeutic Inc, Framingham, MA, United States Institute of Human Virology, University of Maryland, Baltimore, MD, United States Department of Dermatology, Johns Hopkins University, Baltimore, MD, United States Division of Biostatistics, University of Maryland Greenebaum Cancer Center, Baltimore, MD, United States Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States * Corresponding author; email: sstrome{at}smail.umaryland.edu. CD137 (4-1BB) is a co-stimulatory molecule which can be manipulated for the treatment of cancer and autoimmune disease. While agonistic antibodies (mAb's) against CD137 enhance the rejection of murine tumors in a natural killer (NK) and T cell dependent fashion, the mechanism for NK dependence is poorly understood. In this study, we evaluated the ability of two different glycoforms of a chimerized anti-human CD137 mAb, an aglycosylated (GA) and a low fucose form (GG), to react with human NK cells. Both mAb's bound similarly to CD137, were competitively inhibited by the parental mAb and partially blocked the interaction between CD137 and CD137Ligand. 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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