Bypassing glycosylation: engineering aglycosylated full-length IgG antibodies for human therapy

Abstract

In recent years a number of aglycosylated therapeutic antibodies have entered the clinic. The clinical evaluation of these antibodies has served to dispel concerns that the absence of the ubiquitous N297 glycan in the Fc of IgG might result in immunogenicity, poor in vivo stability or unfavorable pharmacokinetics. Importantly, recent studies have now demonstrated that aglycosylated antibodies can be engineered to display novel effector functions and mechanisms of action that do not appear to be possible with their glycosylated counterparts. Moreover, the ability to manufacture aglycosylated antibodies in lower eukaryotes or in bacteria provides significant bioprocessing advantages in terms of shorter bioprocess development and running times and by completely bypassing the problems associated with the glycan heterogeneity of conventional antibodies. These advantages are poised to catapult aglycosylated antibodies to the forefront of protein therapeutics.