| Literature DB >> 21251615 |
Nicholas S Wilson1, Becky Yang, Annie Yang, Stefanie Loeser, Scot Marsters, David Lawrence, Yun Li, Robert Pitti, Klara Totpal, Sharon Yee, Sarajane Ross, Jean-Michel Vernes, Yanmei Lu, Cam Adams, Rienk Offringa, Bob Kelley, Sarah Hymowitz, Dylan Daniel, Gloria Meng, Avi Ashkenazi.
Abstract
Antibodies to cell-surface antigens trigger activatory Fcγ receptor (FcγR)-mediated retrograde signals in leukocytes to control immune effector functions. Here, we uncover an FcγR mechanism that drives antibody-dependent forward signaling in target cells. Agonistic antibodies to death receptor 5 (DR5) induce cancer-cell apoptosis and are in clinical trials; however, their mechanism of action in vivo is not fully defined. Interaction of the DR5-agonistic antibody drozitumab with leukocyte FcγRs promoted DR5-mediated tumor-cell apoptosis. Whereas the anti-CD20 antibody rituximab required activatory FcγRs for tumoricidal function, drozitumab was effective in the context of either activatory or inhibitory FcγRs. A CD40-agonistic antibody required similar FcγR interactions to stimulate nuclear factor-κB activity in B cells. Thus, FcγRs can drive antibody-mediated receptor signaling in target cells. Copyright ÂEntities:
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Year: 2011 PMID： 21251615 DOI： 10.1016/j.ccr.2010.11.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743