期刊
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
卷 111, 期 4, 页码 391-396出版社
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2010.12.007
关键词
Antibody; Antibody-dependent cellular cytotoxicity; Antibody-dependent cellular phagocytosis; Fc gamma receptor; Monoclonal antibody with tandemly repeated Fc domains; CD20
We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fry receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fc gamma receptor-blocking study demonstrated that T3-Ab mediated ADCP via both Fr gamma RIA and Fr gamma RIIA. whereas M-Ab mediated ADCP exclusively via Fr gamma RIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. (C) 2010, The Society for Biotechnology, Japan. All rights reserved.
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