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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2648-2654. Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2006-04-020057. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-020057v1 108/8/2648    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 Bowles, J. A. Articles by Weiner, G. J. Search for Related Content PubMed PubMed Citation Articles by Bowles, J. A. Articles by Weiner, G. J. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab Julie A. Bowles, Siao-Yi Wang, Brian K. Link, Barrett Allan, Gregory Beuerlein, Mary-Ann Campbell, David Marquis, Brian Ondek, James E. Wooldridge, Brian J. Smith, James B. Breitmeyer, and George J. Weiner From the Holden Comprehensive Cancer Center, the Department of Internal Medicine, the Graduate Program in Immunology, and the Department of Biostatistics, University of Iowa, Iowa City; and Applied Molecular Evolution, San Diego, CA. Growing evidence indicates that the affinity of monoclonal antibodies (mAbs) for CD16 (FcRIII) plays a central role in the ability of the mAb to mediate antitumor activity. We evaluated how CD16 polymorphisms, and mAb with modified affinity for target antigen and CD16, affect natural killer (NK) cell phenotype when CD20+ malignant B cells were also present. The mAb consisted of rituximab (R), anti-CD20 with enhanced affinity for CD20 (AME-B), and anti-CD20 with enhanced affinity for both CD20 and CD16 (AME-D). Higher concentrations of mAb were needed to induce CD16 modulation, CD54 up-regulation, and antibody-dependent cellular cytotoxicity (ADCC) on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with AME-D irrespective of CD16 polymorphism. At saturating mAb concentrations, peak NK activation was greater for AME-D. Similar results were found with measurement of CD16 modulation, CD54 up-regulation, and ADCC. These data demonstrate that cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and they provide further evidence for the clinical development of such mAbs with the goal of improving clinical response to mAb. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Zalevsky, I. W. L. Leung, S. Karki, S. Y. Chu, E. A. Zhukovsky, J. R. Desjarlais, D. F. Carmichael, and C. E. Lawrence The impact of Fc engineering on an anti-CD19 antibody: increased Fc{gamma} receptor affinity enhances B-cell clearing in nonhuman primates Blood, April 16, 2009; 113(16): 3735 - 3743. [Abstract] [Full Text] [PDF] M. Peipp, T. Schneider-Merck, M. Dechant, T. Beyer, J. J. Lammerts van Bueren, W. K. Bleeker, P. W. H. I. Parren, J. G. J. van de Winkel, and T. Valerius Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations J. Immunol., March 15, 2008; 180(6): 4338 - 4345. [Abstract] [Full Text] [PDF] N. Congy-Jolivet, A. Bolzec, D. Ternant, M. Ohresser, H. Watier, and G. Thibault Fc{gamma}RIIIa Expression Is Not Increased on Natural Killer Cells Expressing the Fc{gamma}RIIIa-158V Allotype Cancer Res., February 15, 2008; 68(4): 976 - 980. [Abstract] [Full Text] [PDF] S.-Y. Wang, E. Racila, R. P. Taylor, and G. J. Weiner NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement Blood, February 1, 2008; 111(3): 1456 - 1463. [Abstract] [Full Text] [PDF] E. Hatjiharissi, L. Xu, D. D. Santos, Z. R. Hunter, B. T. Ciccarelli, S. Verselis, M. Modica, Y. Cao, R. J. Manning, X. Leleu, et al. Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIa-158 V/V and V/F polymorphism Blood, October 1, 2007; 110(7): 2561 - 2564. [Abstract] [Full Text] [PDF]

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