Production of therapeutic antibodies with controlled fucosylation

Abstract

The clinical success of therapeutic antibodies is demonstrated by the number of antibody therapeutics that have been brought to market and the increasing number of therapeutic antibodies in development. Recombinant antibodies are molecular-targeted therapeutic agents and represent a major new class of drugs. However, it is still very important to optimize and maximize the clinical efficacy of therapeutic antibodies, in part to help lower the cost of therapeutic antibodies by potentially reducing the dose or the duration of treatment. Clinical trials using therapeutic antibodies fully lacking core fucose residue in the Fc oligosaccharides are currently underway, and their remarkable physiological activities in humans in vivo have attracted attention as next-generation therapeutic antibody approaches with improved efficacy. Thus, an industrially applicable antibody production process that provides consistent yields of fully nonfucosylated antibody therapeutics with fixed quality has become a key goal in the successful development of next-generation therapeutic agents. In this article, we review the current technologies for production of therapeutic antibodies with control of fucosylation of the Fc N-glycans.

Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study

“…24 In general, the absence of fucose has been shown to increase the affinity for Fcγ receptor IIIa and to enhance FcγRIIIa-mediated ADCC. 25,26 The role of ADCC in trastuzumab efficacy is not entirely understood. Preclinical studies indicate that increasing the ADCC activity of trastuzumab can result in increased anti-tumor efficacy.…”

EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity

“…10 The control of IgG fucosylation is thus one of the promising approaches currently under active investigation to improve the potency of therapeutic antibodies and possibly reduce costs. Production of non-fucosylated therapeutic antibodies has been mostly achieved through glycoengineering strategies in CHO cells, 11 but some species naturally have the capability to produce glycoproteins with low fucose. Raju et al 12 reported that chicken IgG1 contain complex glycans with naturally reduced fucose content compared to other species.…”

A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

“…18,25 The therapeutic anticancer potential of antibodies with decreased fucosylation, however, has been well recognized, and their power is currently being harnessed in clinical trials. 18,[20][21][22][23][24][26][27][28][29][30] In whites, the main antibodies causing FNAIT are the anti-human platelet antigen (HPA) 1a antibodies, found in ;85% of the cases and in ;1:1500 pregnancies. [31][32][33] The HPA-1a epitope resides in the GPIIIa protein of the GPIIb/IIIa complex and is missing in individuals with a single nucleotide polymorphism resulting in an L to P change at position 33 in the mature protein.…”