Defucosylated Antibodies Engineering Service

Human IgG1 isotype antibodies are usually used therapeutically, which contains two diantenna complex N-linked oligosaccharides in the constant region (Fc). Especially with regard to cancer treatment, it is known that the antibody effector function of antibody-dependent cellular cytotoxicity (ADCC) is very important and is closely related to the clinical efficacy of humans in vivo. ADCC is greatly enhanced by the absence of the core fucose of oligosaccharides attached to the Fc. Unfortunately, all licensed therapeutic antibodies and almost all currently developed therapeutic antibodies are fucosylated and fail to optimize ADCC, which leads to unwanted immunogenic response and weak efficacy. At Creative Biolabs, we explored the possibility of transforming established antibody-producing cells into cells that completely lack core fucosylated antibodies to promote the rapid development of next-generation therapeutic antibodies.

Biological activity of core fucose residue

The effect of fucose consumption of IgG-Fc glycans on ADCC may represent one of the most important discoveries in antibody glycobiology. The significant enhancement of ADCC is attributed to the increased affinity of non-fucosylated IgG for FcγRIIIa expressed on natural killer (NK) cells. Although it has been shown that the deletion of core fucose residues in Fc glycans can significantly improve the binding of antibodies to FcRIIIa and ADCC activity, many studies have shown that the level of fucosylation has a slight effect on the binding of antibodies to FcγR1, FcγRII and C1q. It has been reported in previous studies that, compared with fucosylated recombinant IgG, fucosylated anti-HER2 exhibited about 100 times higher ADCC. Studies have confirmed that non-fucosylated IgG1 mediates very high ADCC in humans at low doses, thereby enhancing the therapeutic potential of modified mAbs. Another study showed that the higher binding affinity of fucosylated IgG to FcγRIIIa is applicable to all IgG subclasses. In summary, the fucosylation of mAb has the greatest impact on ADCC enhancement, which mediates the efficacy of potential therapeutic recombinant antibodies.

Glycoengineering Serivices

In order to support our mission to achieve the frontier advancement in life sciences, Creative Biolabs has developed many cutting-edge technologies in the field of glycan engineering based on our platform. Through modern recombinant technology, a group of specific glycosyltransferase and/or glycosidase genes can be specifically knocked out or adjusted to produce glycoengineered antibodies with more humanization and homogenous glycosylation, better pharmacokinetics and enhanced pharmacological efficacy. Our scientists are fully confident to provide effective and economically feasible antibody glycoengineering solutions.

Please feel free to send us your project description and requirements, and you will get customized all-in-one services to meet your R&D production needs.