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Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nagashima, Hiroaki Ootsubo, Michiko Fukazawa, Mizuki Motoi, Sotaro Konakahara, Shu Masuho, Yasuhiko
Description	Country affiliation: Japan Author Affiliation: Nagashima H ( Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510, Japan. nagashimahra@chugai-pharm.co.jp)
Abstract	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 FcÎ³ 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 FcÎ³ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcÎ³RIA and FcÎ³RIIA, whereas M-Ab mediated ADCP exclusively via FcÎ³RIA. 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.
File Format	HTM / HTML
ISSN	13891723
Issue Number	4
Volume Number	111
e-ISSN	13474421
Journal	Journal of Bioscience and Bioengineering
Language	English
Publisher	Elsevier
Publisher Date	2011-04-01
Publisher Place	Japan
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Biomedical Engineering Discipline Microbiology Antibodies, Monoclonal Chemistry Physiology Immunoglobulin Fc Fragments Phagocytosis Genetics Antigens, Cd20 Immunology Cell Line, Tumor Flow Cytometry Humans Immunoglobulins, Intravenous Monocytes Drug Effects Protein Structure, Tertiary Receptors, Igg Recombinant Fusion Proteins Repetitive Sequences, Amino Acid Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Bioengineering Applied Microbiology and Biotechnology Biotechnology

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