An Fcγ Receptor-Dependent Mechanism Drives Antibody-Mediated Target-Receptor Signaling in Cancer Cells

被引：227

作者：

Wilson, Nicholas S. ^{[1
]}

Yang, Becky ^{[1
]}

Yang, Annie ^{[1
]}

Loeser, Stefanie ^{[2
]}

Marsters, Scot ^{[1
]}

Lawrence, David ^{[1
]}

Li, Yun ^{[1
]}

Pitti, Robert ^{[1
]}

Totpal, Klara ^{[3
]}

Yee, Sharon ^{[3
]}

Ross, Sarajane ^{[3
]}

Vernes, Jean-Michel ^{[4
]}

Lu, Yanmei ^{[4
]}

Adams, Cam ^{[5
]}

Offringa, Rienk ^{[2
]}

Kelley, Bob ^{[5
]}

Hymowitz, Sarah ^{[6
]}

Daniel, Dylan ^{[1
]}

Meng, Gloria ^{[4
]}

Ashkenazi, Avi ^{[1
]}

机构：

[1] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Discovery Immunol, San Francisco, CA 94080 USA

[3] Genentech Inc, Dept Canc Signaling & Translat Oncol, San Francisco, CA 94080 USA

[4] Genentech Inc, Dept Assay & Automat Technol, San Francisco, CA 94080 USA

[5] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA

[6] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA

来源：

CANCER CELL | 2011年 / 19卷 / 01期

关键词：

ANTI-CD20; MONOCLONAL-ANTIBODY; IN-VIVO; THERAPEUTIC ANTIBODIES; CELLULAR CYTOTOXICITY; TUMOR-CELL; ESTABLISHED TUMORS; APOPTOSIS; IGG; DEATH; POLYMORPHISMS;

D O I：

10.1016/j.ccr.2010.11.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Antibodies to cell-surface antigens trigger activatory Fc gamma receptor (Fc gamma R)-mediated retrograde signals in leukocytes to control immune effector functions. Here, we uncover an Fc gamma R 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 Fc gamma Rs promoted DR5-mediated tumor-cell apoptosis. Whereas the anti-CD20 antibody rituximab required activatory Fc gamma Rs for tumoricidal function, drozitumab was effective in the context of either activatory or inhibitory Fc gamma Rs. A CD40-agonistic antibody required similar Fc gamma R interactions to stimulate nuclear factor-kappa B activity in B cells. Thus, Fc gamma Rs can drive antibody-mediated receptor signaling in target cells.

引用

页码：101 / 113

页数：13

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