Creative Biolabs established the GlycoOpitimize™ platform to integrate our multiple cutting-edge techniques for antibody glycoengineering. We now provide our clients all over the world with low- or non-fucosylated antibodies service. Our one-stop service packages include but not limited to antibody production, cell line development, biopharmaceutical process development and glycan analysis.
It has been repeatedly reported in various therapeutic mAbs that removal of the core α1,6-linked fucose residues from Fc glycans can significantly increase the Fc binding affinity for the activatory Fcγ receptor IIIa (FcγR IIIa) with a dramatic enhanced antibody-dependent cellular cytotoxicity (ADCC). ADCC is one of the most important mechanisms responsible for the efficacy of mAbs in cancer therapies, therefore low- or non-fucosylated antibodies are more potent than their fucosylated counterparts. Crystallography studies showed that the fucose residues of Fc inhibit the carbohydrate-carbohydrate interactions between the N-glycan attached to the Asn162 of FcγRIIIa and the core pentasaccharide of Fc glycan, and the fucose residues can also limit the conformational adaptation of FcγRIIIa Tyr296 for the formation of a high-affinity complex. Depletion of the core fucose residues from the Fc glycans can lead to an enhanced affinity between the Fc and FcγRIIIa and then allows a more efficient activation of FcγRIIIa-bearing NK cells and macrophages. Multiple methods have been used to produce low- or non-fucosylated antibodies. Among them, the most widely used method is to produce glyco-optimized antibodies in bio-engineered cell lines. For example, FUT8 gene (encodes the α1,6-fucosyltransferase) knockout CHO cell line (Kyowa Kirin Hakko), CHO cell line that overexpresses β1,4-GlcNAc transferase III (GnT III) (Glycart, Roche), Pichia pastoris (GlycoFi, Merck) and so on.
Based on our GlycoOpitimize™ platform, we offer a perfect set of low- or non-fucosylated antibodies service. Production systems including mammalian cell lines (CHO, NS0 and SP2/0), yeasts (Pichia pastoris, Saccharomyces cerevisiae and Saccharomyces cerevisiae), baculovirus-infected insect cells, avian cells (Duck embryonic stem cells), plant cells (lemna minor, Physcomitrella patens and tobacco) and so on are all available for our clients. Our service varies from antibody production for research quantities or in large scale, cell line development to downstream biopharmaceutical processes development. Also antibody glycan analysis service is included.
Le NP, Bowden TA, et. al. (2016) Immune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies, Biochimica et Biophysica Acta, 1860(8), 1655-1668.