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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1205-1213. Prepublished online as a Blood First Edition Paper on May 21, 2008; DOI 10.1182/blood-2008-01-135160. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-01-135160v1 112/4/1205    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 Minard-Colin, V. Articles by Tedder, T. F. Search for Related Content PubMed PubMed Citation Articles by Minard-Colin, V. Articles by Tedder, T. F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 23, 2008 Accepted April 17, 2008 Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcRI, FcRIII, and FcRIV Veronique Minard-Colin, Yan Xiu, Jonathan C. Poe, Mayuka Horikawa, Cynthia M. Magro, Yasuhito Hamaguchi, Karen M. Haas, and Thomas F. Tedder* Department of Immunology, Duke University Medical Center, Durham, NC, United States Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, United States * Corresponding author; email: thomas.tedder{at}duke.edu. Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular mechanisms responsible for lymphoma killing by CD20 mAb in a homologous system amenable to mechanistic studies and genetic manipulation, a mouse lymphoma model was developed using primary tumor cells from a C57BL/6 Eµ-cMyc transgenic mouse and mouse anti-mouse CD20 mAbs. CD20 mAb treatment of syngeneic mice with adoptively transferred lymphomas prevented tumor development or significantly prolonged mouse survival depending on tumor volume, mAb dose, and treatment timing. Cooperative FcRIV, FcRIII and FcRI interactions mediated optimal lymphoma depletion by CD20 mAb in vivo, while clodronate-mediated depletion of macrophages eliminated the therapeutic benefit of CD20 mAb. Although CD20 mAbs activated complement in vitro and in vivo, normal and malignant B cell depletion was induced through C1q- and C3-independent mechanisms. Thus, the ability of CD20 mAbs to deplete malignant B cells in vivo required FcR-dependent utilization of the innate mononuclear cell immune system. These findings allow for mechanism-based predictions of the biological outcome of CD20 mAb therapy and treatment optimization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Leidi, E. Gotti, L. Bologna, E. Miranda, M. Rimoldi, A. Sica, M. Roncalli, G. A. Palumbo, M. Introna, and J. Golay M2 Macrophages Phagocytose Rituximab-Opsonized Leukemic Targets More Efficiently than M1 Cells In Vitro J. Immunol., April 1, 2009; 182(7): 4415 - 4422. [Abstract] [Full Text] [PDF]

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