In vivo glyco-engineered antibody with improved lytic potential produced by an innovative non-mammalian expression system

Recent studies have demonstrated that the reduction of the core fucosylation on N‐glycans of human IgGs is responsible for a clearly enhanced antibody‐dependent cellular cytotoxicity (ADCC). This finding might give access to improved active therapeutic antibodies. Here, the expression of the tumor a...

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Bibliographic Details
Published in:Biotechnology journal 2007-06, Vol.2 (6), p.700-708
Main Authors: Schuster, Manfred, Jost, Wolfgang, Mudde, Geert C., Wiederkum, Susanne, Schwager, Cornelia, Janzek, Evelyne, Altmann, Friedrich, Stadlmann, Johannes, Stemmer, Christian, Gorr, Gilbert
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - biosynthesis
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Bryopsida - genetics
Bryopsida - metabolism
Effector functions
Genetic Enhancement - methods
Glyco-engineering
Humans
Lewis Y-specific antibody
Moss
Physcomitrella patens
Polysaccharides - metabolism
Protein Engineering - methods
Recombinant antibody expression
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Summary:Recent studies have demonstrated that the reduction of the core fucosylation on N‐glycans of human IgGs is responsible for a clearly enhanced antibody‐dependent cellular cytotoxicity (ADCC). This finding might give access to improved active therapeutic antibodies. Here, the expression of the tumor antigen‐specific antibody IGN311 was performed in a glyco‐optimized strain of the moss Physcomitrella patens. Removal of plant specific N‐glycan structures in this plant expression host was achieved by targeted knockout of corresponding genes and included quantitative elimination of core fucosylation. Antibodies transiently expressed and secreted by such genetically modified moss protoplasts assembled correctly, showed an unaltered antigen‐binding affinity and, in extensive tests, revealed an up to 40‐fold enhanced ADCC. Thus, the glyco‐engineered moss‐based transient expression platform combines a rapid technology with the subsequent analysis of glycooptimized therapeutics with regard to advanced properties.
ISSN:1860-6768
1860-7314
DOI:10.1002/biot.200600255