title: In vivo glyco-engineered antibody with improved lytic potential produced by an innovative non-mammalian expression system.
abstract: 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.
authors.affiliation: Igeneon AG, Vienna, Austria. manfred.schuster@apeiron-biologics.com
authors.forename: Manfred
authors.initials: M
authors.lastname: Schuster
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jost
authors.forename: Geert C
authors.initials: GC
authors.lastname: Mudde
authors.forename: Susanne
authors.initials: S
authors.lastname: Wiederkum
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schwager
authors.forename: Evelyne
authors.initials: E
authors.lastname: Janzek
authors.forename: Friedrich
authors.initials: F
authors.lastname: Altmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Stadlmann
authors.forename: Christian
authors.initials: C
authors.lastname: Stemmer
authors.forename: Gilbert
authors.initials: G
authors.lastname: Gorr
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019068:Bryopsida / Q000235:genetics / Q000378:metabolism*; D024861:Genetic Enhancement / Q000379:methods*; D006801:Humans; D011134:Polysaccharides / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; C510956:IGN 311; D011134:Polysaccharides