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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1793-1800. Prepublished online as a Blood First Edition Paper on June 1, 2004; DOI 10.1182/blood-2004-01-0039. This Article Full Text (PDF) All Versions of this Article: 2004-01-0039v1 104/6/1793    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 Teeling, J. L Articles by Glennie, M. J Search for Related Content PubMed PubMed Citation Articles by Teeling, J. L Articles by Glennie, M. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 7, 2004 Accepted May 2, 2004 Characterisation of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin's lymphomas Jessica L Teeling, Ruth R French, Mark S Cragg, Jeroen van den Brakel, Marielle Pluyter, Haichun Huang, Claude H Chan, Paul W Parren, C E Hack, Michael Dechant, Thomas Valerius, Jan G van de Winkel, and Martin J Glennie* Genmab, Utrecht, The Netherlands Tenovus Cancer Research Laboratory, University of Southampton, Southampton, Hampshire, United Kingdom Medarex, Princeton, NJ, USA Sanquin Research, CLB and VU University Medical Center, Amsterdam, The Netherlands Medicine I, University Schleswig-Holstein, Kiel, Germany Genmab, Utrecht, The Netherlands; Immunotherapy, University of Utrecht, Utrecht, The Netherlands Tenovus Cancer Research Laboratory, University of Southampton, Southampton, Hampshire, United Kingdom; Genmab, Utrecht, The Netherlands * Corresponding author; email: mjg{at}soton.ac.uk. Despite the rapid and widespread integration of chimeric CD20 mAb, rituximab, into the management of non-Hodgkin's lymphoma, its efficacy remains variable and often modest when used as a single agent. To develop more potent reagents, human immunoglobulin-transgenic mice were used to generate a panel of IgG1 CD20 mAb. All reagents bound strongly to CD20+ cells and recruited mononuclear cells for the lysis of malignant B cells. However, two mAb, 2F2 and 7D8, were exceptionally active in complement-dependent cytotoxcity (CDC), being able to lyse a range of rituximab resistant targets, such as CD20-low CLL, in the presence of human plasma or un-fractionated blood. Further analysis showed that 2F2 and 7D8, like rituximab, redistributed CD20 into Triton X-100 insoluble regions of the plasma membrane, but that they had markedly slower slow off-rates. To determine whether off-rate influenced CDC, a non-complement activating F(ab')2 anti-human kappa reagent was used. This reagent markedly slowed the off-rate of rituximab and increased its CDC activity to that of 2F2 and 7D8. Thus, with increasing evidence that mAb therapeutic activity in vivo depends on complement activation, these new CD20 reagents with their slow off-rates and increased potency in CDC hold considerable promise for improved clinical activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CD20 Trek: the next generation Ronald P. Taylor Blood 2004 104: 1592. [Full Text] [PDF] This article has been cited by other articles: P. V. Beum, M. A. Lindorfer, F. Beurskens, P. T. Stukenberg, H. M. Lokhorst, A. W. Pawluczkowycz, P. W. H. I. Parren, J. G. J. van de Winkel, and R. P. Taylor Complement Activation on B Lymphocytes Opsonized with Rituximab or Ofatumumab Produces Substantial Changes in Membrane Structure Preceding Cell Lysis J. Immunol., July 1, 2008; 181(1): 822 - 832. [Abstract] [Full Text] [PDF] C. A. Walshe, S. A. Beers, R. R. French, C. H. T. Chan, P. W. Johnson, G. K. Packham, M. J. Glennie, and M. S. Cragg Induction of Cytosolic Calcium Flux by CD20 Is Dependent upon B Cell Antigen Receptor Signaling J. Biol. Chem., June 20, 2008; 283(25): 16971 - 16984. [Abstract] [Full Text] [PDF] B. Li, S. Shi, W. Qian, L. Zhao, D. Zhang, S. Hou, L. Zheng, J. Dai, J. Zhao, H. Wang, et al. Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity Cancer Res., April 1, 2008; 68(7): 2400 - 2408. [Abstract] [Full Text] [PDF] B. Coiffier, S. Lepretre, L. M. Pedersen, O. Gadeberg, H. Fredriksen, M. H. J. van Oers, J. Wooldridge, J. Kloczko, J. Holowiecki, A. Hellmann, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study Blood, February 1, 2008; 111(3): 1094 - 1100. [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] W. Y. Lin, Q. Gong, D. Seshasayee, Z. Lin, Q. Ou, S. Ye, E. Suto, J. Shu, W. Pun Lee, C.-W. V. Lee, et al. Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade Blood, December 1, 2007; 110(12): 3959 - 3967. [Abstract] [Full Text] [PDF] M. van der Neut Kolfschoten, J. Schuurman, M. Losen, W. K. Bleeker, P. Martinez-Martinez, E. Vermeulen, T. H. den Bleker, L. Wiegman, T. Vink, L. A. Aarden, et al. Anti-Inflammatory Activity of Human IgG4 Antibodies by Dynamic Fab Arm Exchange Science, September 14, 2007; 317(5844): 1554 - 1557. [Abstract] [Full Text] [PDF] P. Cravedi, P. Ruggenenti, M. C. Sghirlanzoni, and G. Remuzzi Titrating Rituximab to Circulating B Cells to Optimize Lymphocytolytic Therapy in Idiopathic Membranous Nephropathy Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 932 - 937. [Abstract] [Full Text] [PDF] A. Kretz-Rommel, F. Qin, N. Dakappagari, E. P. Ravey, J. McWhirter, D. Oltean, S. Frederickson, T. Maruyama, M. A. Wild, M.-J. Nolan, et al. CD200 Expression on Tumor Cells Suppresses Antitumor Immunity: New Approaches to Cancer Immunotherapy J. Immunol., May 1, 2007; 178(9): 5595 - 5605. [Abstract] [Full Text] [PDF] M. J. Leandro, N. Cooper, G. Cambridge, M. R. Ehrenstein, and J. C. W. Edwards Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy Rheumatology, January 1, 2007; 46(1): 29 - 36. [Abstract] [Full Text] [PDF] J. L. Teeling, W. J. M. Mackus, L. J. J. M. Wiegman, J. H. N. van den Brakel, S. A. Beers, R. R. French, T. van Meerten, S. Ebeling, T. Vink, J. W. Slootstra, et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20 J. Immunol., July 1, 2006; 177(1): 362 - 371. [Abstract] [Full Text] [PDF] T. van Meerten, R. S. van Rijn, S. Hol, A. Hagenbeek, and S. B. Ebeling Complement-Induced Cell Death by Rituximab Depends on CD20 Expression Level and Acts Complementary to Antibody-Dependent Cellular Cytotoxicity. Clin. Cancer Res., July 1, 2006; 12(13): 4027 - 4035. [Abstract] [Full Text] [PDF] M. Alfonso-Perez, S. Lopez-Giral, N. E. Quintana, J. Loscertales, P. Martin-Jimenez, and C. Munoz Anti-CCR7 monoclonal antibodies as a novel tool for the treatment of chronic lymphocyte leukemia J. Leukoc. Biol., June 1, 2006; 79(6): 1157 - 1165. [Abstract] [Full Text] [PDF] P. V. Beum, A. D. Kennedy, M. E. Williams, M. A. Lindorfer, and R. P. Taylor The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes J. Immunol., February 15, 2006; 176(4): 2600 - 2609. [Abstract] [Full Text] [PDF] F. Perosa, E. Favoino, M. A. Caragnano, and F. Dammacco Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3b precursor Blood, February 1, 2006; 107(3): 1070 - 1077. [Abstract] [Full Text] [PDF] B. F. Israel, M. Gulley, S. Elmore, S. Ferrini, W.-h. Feng, and S. C. Kenney Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas Mol. Cancer Ther., December 1, 2005; 4(12): 2037 - 2044. [Abstract] [Full Text] [PDF] E A Clark and J A Ledbetter How does B cell depletion therapy work, and how can it be improved? Ann Rheum Dis, November 1, 2005; 64(suppl_4): iv77 - iv80. [Abstract] [Full Text] [PDF] D. G. Maloney Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines J. Clin. Oncol., September 10, 2005; 23(26): 6421 - 6428. [Abstract] [Full Text] [PDF] J. S. Abramson and M. A. Shipp Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach Blood, August 15, 2005; 106(4): 1164 - 1174. [Abstract] [Full Text] [PDF] J. P. Leonard, M. Coleman, J. Ketas, M. Ashe, J. M. Fiore, R. R. Furman, R. Niesvizky, T. Shore, A. Chadburn, H. Horne, et al. Combination Antibody Therapy With Epratuzumab and Rituximab in Relapsed or Refractory Non-Hodgkin's Lymphoma J. Clin. Oncol., August 1, 2005; 23(22): 5044 - 5051. [Abstract] [Full Text] [PDF] S. D. Gillies, Y. Lan, S. Williams, F. Carr, S. Forman, A. Raubitschek, and K.-M. Lo An anti-CD20-IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma Blood, May 15, 2005; 105(10): 3972 - 3978. [Abstract] [Full Text] [PDF] J. P. 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