Premium
Use of 5‐Thio‐L‐Fucose to modulate binding affinity of therapeutic proteins
Author(s) -
Zimmermann Martina,
Nguyen Melanie,
Schultheiss Christian M.,
Kolmar Harald,
Zimmer Aline
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27695
Subject(s) - fucosylation , antibody dependent cell mediated cytotoxicity , fucose , chinese hamster ovary cell , chemistry , antibody , glycan , biochemistry , effector , cell culture , glycosylation , cytotoxicity , microbiology and biotechnology , biology , in vitro , immunology , glycoprotein , receptor , genetics
The reduction of antibody core‐fucosylation is known to enhance antibody‐dependent cellular cytotoxicity (ADCC). In this study, 5‐Thio‐ l ‐Fucose (ThioFuc) was investigated as a media and feed supplement for modulating the fucosylation profile of therapeutic proteins and, thereby, improving the resulting effector functions. Glycan analysis of five different therapeutic proteins produced by a diverse set of Chinese hamster ovary cell lines demonstrated a clone dependent impact of ThioFuc treatment. Using rituximab as a model, an efficient dose‐ and time‐dependent reduction of core‐fucosylation up to a minimum of 5% were obtained by ThioFuc. Besides a concomitant increase in the afucosylation level up to 48%, data also revealed up to 47% incorporation of ThioFuc in place of core‐fucosylation. In accordance with the glycan data, antibodies produced in the presence of ThioFuc revealed an enhanced FcγRIIIa binding up to 7.7‐fold. Furthermore, modified antibodies subjected to a cell‐based ADCC reporter bioassay proved to exert both a 1.5‐fold enhanced ADCC efficacy and 2.6‐fold enhancement in potency in comparison to their native counterparts—both of which contribute to an improvement in the ADCC activity. In conclusion, ThioFuc is a potent fucose derivative with potential applications in drug development processes.