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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4170-4177. Prepublished online as a Blood First Edition Paper on June 26, 2008July 10, 2008; DOI 10.1182/blood-2008-04-149161. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-149161v1 blood-2008-04-149161v2 112/10/4170    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Beers, S. A Articles by Glennie, M. J Search for Related Content PubMed PubMed Citation Articles by Beers, S. A Articles by Glennie, M. J Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 4, 2008 Accepted June 3, 2008 Type II (tositumomab) anti-CD20 monoclonal antibody out performs Type I (rituximab-like) reagents in B-cell depletion regardless of complement activation Stephen A Beers, Claude HT Chan, Sonya James, Ruth R French, Kathrine E Attfield, Claire M Brennan, Anupama Ahuja, Mark J Shlomchik, Mark S Cragg, and Martin J Glennie* Tenovus Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton, Hampshire, United Kingdom Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, United States * Corresponding author; email: mjg{at}soton.ac.uk. Anti-CD20 mAb are classified into Type I (rituximab-like) or Type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare Type I and II mAb directly in vivo and maximize Fc effector function, we selected and engineered mAb with the same mouse IgG2a isotype and assessed their B cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonising activity for phagocytosis, and in-vivo half-life, the Type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the Type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular the spleen. Failure to engage complement did not explain the efficacy of the Type II reagents, since Type I mAb mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of Type II CD20 mAb in human B cell diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Complement activation impacts B-cell depletion by both type I and type II CD20 monoclonal antibodies Frank J. Beurskens, Sigrid R. Ruuls, Patrick J. Engelberts, Tom Vink, Wendy J. Mackus, Jan G. J. van de Winkel, and Paul W. H. I. Parren Blood 2008 112: 4354-4355. [Full Text] [PDF] Response: Superior B cell–depleting activity of type II anti-CD20 mAb is not due to activation of complement Stephen A. Beers, Mark S. Cragg, and Martin J. Glennie Blood 2008 112: 4355-4356. [Full Text] [PDF]

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