Glyco-Engineering of Human IgG-Fc to Modulate Biologic Activities

Title:Glyco-Engineering of Human IgG-Fc to Modulate Biologic Activities

Volume: 17 Issue: 15

Author(s): Roy Jefferis

Affiliation:

Keywords: Antibody therapeutics, cost-of-treatment, effector functions, function, glycosylation, human IgG structure, IgG subclasses, recombinant antibodies, solubility, stability.

Abstract: Advances in genetic and protein engineering and the ability to maintain proliferating mammalian cells in vitro, has allowed reverse engineering of antibodies, i.e. generation of antibodies having specificity for self-antigens. Thus, the lethal consequence of horror autotoxicus, anti-self-responses as envisaged by Paul Ehrlich (1854-1915), has been turned to advantage for treatment of multiple disease states. In order to reap these benefits, it is essential that, in addition to target specificity, the antibody is customised to deliver appropriate downstream biologic effector activities. Genetic engineering allows the development of any chosen isotype; however, The IgG class predominates in human serum and the majority of monoclonal antibody (mAb) therapeutics are based on the IgG format. This review focuses on the structure and function of the four human IgG isotypes (subclasses) and the biologic functions that their immune complexes activate through interactions with cellular Fc receptors (FcγR & FcRn) and/or the C1q component of complement. The long catabolic half-life (~21 days) of IgG contributes to its efficacy as a therapeutic. Each human IgG subclass exhibits a unique profile of biologic activities that are dependent on the glycoform profile of the IgG-Fc. Our current understanding of IgG structure/function relationships allows protein and glycosylation engineering of the IgG-Fc to enhance or eliminate biologic activities and the generation of therapeutics optimal for a given disease indication.

Cite this article as:

Jefferis Roy, Glyco-Engineering of Human IgG-Fc to Modulate Biologic Activities, Current Pharmaceutical Biotechnology 2016; 17 (15) . https://dx.doi.org/10.2174/1389201017666161029225929