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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2390-2399. Prepublished online as a Blood First Edition Paper on June 19, 2008; DOI 10.1182/blood-2008-03-144600. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-03-144600v1 112/6/2390    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 Peipp, M. Articles by Valerius, T. Search for Related Content PubMed PubMed Citation Articles by Peipp, M. Articles by Valerius, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 11, 2008 Accepted May 7, 2008 Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells Matthias Peipp, Jeroen J. Lammerts van Bueren, Tanja Schneider-Merck, Wim W.K. Bleeker, Michael Dechant, Thomas Beyer, Roland Repp, Patrick H.C. van Berkel, Tom Vink, Jan G.J. van de Winkel, Paul W.H.I. Parren, and Thomas Valerius* Division of Stem Cell Trans-plantation and Immunotherapy, Christian-Albrechts-University Kiel, Kiel, Germany Genmab BV, Utrecht, Netherlands Division of Nephrology and Hypertension, Christian-Albrechts-University Kiel, Kiel, Germany Immunotherapy Laboratory, Dept. of Immunology, University Medical Center, Utrecht, Utrecht, Netherlands * Corresponding author; email: valerius{at}nephro.uni-kiel.de. Glycosylation of the antibody Fc fragment is essential for Fc receptor-mediated activity. Carbohydrate heterogeneity is known to modulate the activity of effector cells in the blood, in which fucosylation particularly affects NK-cell mediated killing. Here, we investigated how the glycosylation profile of 2F8, a human IgG1 monoclonal antibody (mAb) against EGF-R in clinical development, impacted effector function. Various 2F8 batches differing in fucosylation, galactosylation and sialylation of the complex-type oligosaccharides in the Fc fragment were investigated. Our results confirmed that low fucose levels enhance MNC-mediated ADCC. In contrast, PMN were found to preferentially kill via high-fucosylated antibody. Whole blood ADCC assays, containing both types of effector cells, revealed little differences in tumor cell killing between both batches. Significantly, however, high-fucose antibody induced superior ADCC in blood from G-CSF-primed donors containing higher numbers of activated PMN. In conclusion, our data demonstrated for the first time that lack of fucose does not generally increase the ADCC activity of therapeutic antibodies, and that the impact of Fc glycosylation on ADCC is critically dependent on the recruited effector cell type. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Hossler, S. F Khattak, and Z. J. Li Optimal and consistent protein glycosylation in mammalian cell culture Glycobiology, September 1, 2009; 19(9): 936 - 949. [Abstract] [Full Text] [PDF]

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