Biologics: structural heterogeneity and immunogenicity.

ABSTRACT

In 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.