As one of the well-known service providers in the biotechnology field, Creative Biolabs has years of experience in supplying a broad range of optimized platforms particularly in therapeutic antibody development for global researchers. Currently, we have successfully established and commercialized a wide spectrum of functional assays to illustrate antibody bioactivity and mechanism of action. Particularly, we offer this unique opportunity for our worldwide customers to adopt impeccable Fc engineering service. Especially, the engineering of non-glycosylated IgGs provides a new approach to the design of therapeutic antibodies with tailored functions.
Glycosylation is a key function of the biosynthesis-secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. In recent decades, protein-based therapies have greatly expanded the field of molecular pharmacology due to their outstanding therapeutic potential. Glycosylation of proteins is a complex and versatile post-translational modification that affects biological activity, protein conformation, stability, solubility, secretion, pharmacokinetics, and antigenicity. The IgG molecule carries an oligosaccharide linked to the asparagine residue at position 297 (N297) of the Fc region, and the oligosaccharides play an important role in Fc effector function, including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) which are among the mechanism of action of therapeutic antibodies. Therefore, the engineering of Fc glycosylation is a reasonable strategy to increase the safety and efficacy of therapeutic IgG antibodies.
Fig.1 The glycosylation types in antibody.1
Monoclonal antibodies (mAbs) with high selectivity and specificity constitute a large and growing segment of the bio-therapeutic market. Antibody glycosylation has been associated with antibody characteristics and therapeutic performance. Antibodies with specific glycoforms have been generated to achieve better effector functions, such as afucosylated antibodies that are proved to show stronger ADCC activity. However, in some cases, antibody effector functions are not required as is the case for neutralizing, antagonistic antibodies, which makes it logical to select non-glycosylated or simplified glycosylated antibodies. The use of deglycosylated IgG antibodies has shown various advantages:
Deglycosylation of circular IgG in vivo by administration of an endoglycosidase from Streptococcus pyogenes (Endo-S) is considered to be a novel therapeutic strategy for immune evasion in patients with autoimmune diseases. Moreover, non-glycosylated antibodies can be produced by mutation in E. coli or by mutation of Asn297 to Ala or Gln. Several deglycosylated IgG or Fc platforms have been approved and some candidates are undergoing clinical trials. In addition, Creative Biolabs can simplify glycosylation by shortening the N-glycosylation pathway in the Golgi by knocking out and knocking out specific glycosyltransferases or glycosidases. Simplified glycosylated antibodies have been reported to have similar folding and stability characteristics while having low initial serum clearance and reduced effector function relative to wild-type antibodies.
Fig.2 N-glycan remodel on therapeutic IgG antibodies.2
Besides, we have developed our powerful Antibody GlycoOpitimize™ Platform for optimization of antibody glycosylation, including fucosylation, sialylation, galactosylation, etc.
Creative Biolabs has successfully integrated and commercialized a full range of well-established assays for precisely elaborating functional profiles of therapeutic antibodies. We are always pleased to support scientific research with a high-quality presentation of assay results and satisfy each demand from customers. For more detailed information, please feel free to contact us or directly sent us an inquiry.
References
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