Monoclonal antibodies (mAbs) are important therapeutic agents and have been used for the treatment of many diseases, including infectious and inflammatory diseases, and cancer. The N-linked glycan profiles of mAb therapeutics significantly affect antibody biological functions and a key step in the bioprocess development of mAbs involves the optimization and control of N-glycan profiles. Creative Biolabs, as an expert in antibody development, has built an Antibody GlycoOpitimize Platform to optimize antibody characteristics and improve antibody performance as well as to successfully produce more homogeneously glycosylated antibodies.
Glycosylation of the conserved asparagine residue in each heavy chain of IgG in the CH2 domain is known as N-glycosylation. It is one of the most common post-translational modifications (PTMs) and important critical quality attributes (CQAs) of mAb therapeutics. At this site, variable addition of fucose, bisecting GlcNAc, galactose, and sialic acid residues to the core complex biantennary heptasaccharide (GlcNAc2Man3GlcNAc2) results in the highly heterogeneous characteristics of mAb antibodies.
The N-glycan moiety of IgG-Fc has a significant impact on multifaceted properties of antibodies such as in their effector function, structure, and stability. More specifically, the composition of the Fc N-glycan modulates effector functions such as the antibody-dependent cell mediated cytotoxicity (ADCC), and the complement-dependent cytotoxicity (CDC). Moreover, the effects of the Fc N-glycosylation on antibody safety and pharmacokinetics have also been reported. Therefore, the engineering of Fc glycosylation is a rational strategy to improve the safety and efficacy of therapeutic IgG antibodies.
Fig.1 Glycosylation of the Fc region of IgG antibodies.1
Creative Biolabs has built an antibody GlycoOpitimize platform aiming to better investigate the biological and functional relevance of glycosylation, as well as to optimize antibody therapeutic activity. The glycooptimization can be divided into several types:
Genetic GlycoOpitimization always focuses on the introduction of additional glycosylation motifs into the existing amino acid sequence. In this case, an increased degree of sialylation can be obtained in the hyper-glycosylated variant of human EPO, which results in longer serum half-life.
This approach is designed for the host cell lines to achieve a modified and customized glycosylation pattern. According to the introduction or deletion of the DNA sequences relevant for the desired glycosylation, the genetically modified organism is obtained. In addition, it is also possible to screen the cell populations for genetic defects in their glycosylation machinery.
Metabolic glycooptimization, also known as metabolic oligosaccharide optimization, is a straightforward strategy to create modified glycans by incorporation of exogenously supplied monosaccharides via salvage pathway. This method holds immense potential to manipulate the glycan decoration of selected proteins and result in increased glycoprotein quality.
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