Antibodies are typical examples of biopharmaceuticals which are composed of numerous, almost infinite numbers of potential molecular entities called variants or isoforms, which constitute the microheterogeneity of these molecules. These variants are generated during biosynthesis by so-called posttranslational modification, during purification or upon storage. The variants differ in biological properties such as pharmacodynamic properties, for example, Antibody Dependent Cellular Cytotoxicity, complement activation, and pharmacokinetic properties, for example, serum half-life and safety. Recent progress in analytical technologies such as various modes of liquid chromatography and mass spectrometry has helped to elucidate the structure of a lot of these variants and their biological properties. In this review the most important modifications (glycosylation, terminal modifications, amino acid side chain modifications, glycation, disulfide bond variants and aggregation) are reviewed and an attempt is made to give an overview on the biological properties, for which the reports are often contradictory. Even though there is a deep understanding of cellular and molecular mechanism of antibody modification and their consequences, the clinical proof of the effects observed in vitro and in vivo is still not fully rendered. For some modifications such as core-fucosylation of the N-glycan and aggregation the effects are clear and should be monitored, but with others such as C-terminal lysine clipping the reports are contradictory. As a consequence it seems too early to tell if any modification can be safely ignored.
Keywords: IgG; immunoglobulin; isoforms; monoclonal; pharmacodynamics; pharmacokinetic; safety; variants.
© 2017 The Authors. Biotechnology Journal Published by Wiley-VCHVerlag GmbH & Co. KGaA, Weinheim.