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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3959-3967. Prepublished online as a Blood First Edition Paper on August 8, 2007; DOI 10.1182/blood-2007-04-088088. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-088088v1 110/12/3959    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lin, W. Y. Articles by Martin, F. Search for Related Content PubMed PubMed Citation Articles by Lin, W. Y. Articles by Martin, F. Related Collections Immunotherapy Free Research Articles Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade Wei Yu Lin1, Qian Gong1, Dhaya Seshasayee1, Zhonghua Lin1, Qinglin Ou1, Shiming Ye1, Eric Suto1, Jean Shu1, Wyne Pun Lee1, Ching-Wei V. Lee2, Germaine Fuh2, Maya Leabman3, Suhasini Iyer3, Kathy Howell3, Thomas Gelzleichter3, Joseph Beyer3, Dimitry Danilenko4, Sherry Yeh5, Laura E. DeForge5, Allen Ebens6, Jeffrey S. Thompson7, Christine Ambrose7, Mercedesz Balazs1, Melissa A. Starovasnik2, and Flavius Martin1 Departments of1 Immunology, 2 Protein Engineering, 3 Development Sciences, 4 Pathology, 5 Assay and Automation Technology, and 6 Translational Oncology, Genentech, South San Francisco, CA; and 7 Department of Gene Discovery, Biogen IDEC, Cambridge Center, Cambridge, MA Removal of pathogenic B lymphocytes by depletion of monoclonal antibodies (mAbs) or deprivation of B-cell survival factors has demonstrated clinical benefit in both oncologic and immunologic diseases. Partial clinical responses and emerging data demonstrating incomplete B-cell depletion after immunotherapy fuels the need for improved therapeutic modalities. Lessons from the first generation of therapeutics directed against B-cell-specific antigens (CD20, CD22) are being applied to develop novel antibodies with additional functional attributes. We describe the generation of a novel class of B-cell-directed therapy (anti-BR3 mAbs) that combines the depleting capacity of a therapeutic mAb and blockade of B-cell-activating factor (BAFF)–BR3 B-cell survival. In mice, treatment with antagonistic anti-BR3 antibodies results in quantitatively greater reduction in some B-cell subsets and qualitatively different effects on bone marrow plasma cells compared with BR3-Fc BAFF blockade or with anti-CD20 treatment. Comparative analysis of BR3-Fc and anti-BR3 mAb reveals a lower B-cell dependence for BAFF-mediated survival in nonhuman primates than in mice. This novel class of B-cell-targeted therapies shows species characteristics in mice and primates that will guide translation to treatment of human disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Combination biologics: 1 stone, 2 birds Robert Eisenberg Blood 2007 110: 3817. [Full Text] [PDF]

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