• Brit J Hosp Med · Aug 2017

    Review

    Biologics: structural heterogeneity and immunogenicity.

    • Roy Jefferis.
    • Emeritus Professor, Institute of Immunology and Immunotherapy, University of Birmingham College of Medical and Dental Sciences, Birmingham B15 2TT.
    • Brit J Hosp Med. 2017 Aug 2; 78 (8): 443-447.

    AbstractIn principle the whole human proteome is available for the generation of recombinant proteins and glycoproteins that may serve as drugs (biologics). Endogenous human proteins and glycoproteins are structurally heterogeneous but are recognized as self by the immune system; however, recombinant protein and glycoprotein molecules are necessarily produced in heterologous systems and may include structural variants that are non-self and potentially immunogenic. The addition of human type oligosaccharides may be critical to function while the addition of non-human sugar residues can render biologics immunogenic. A particular concern is the structure of oligosaccharides attached by the hamster and murine cell lines that provide the dominant production platform. Critical structure and function properties that contribute to optimization of therapeutic potential are illustrated through recombinant erythropoietin and antibody therapeutics.

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