Alteration of Physicochemical Properties for Antibody-Drug Conjugates and Their Impact on Stability

J Pharm Sci. 2020 Jan;109(1):161-168. doi: 10.1016/j.xphs.2019.08.006. Epub 2019 Aug 10.

Abstract

Antibody conjugates, in particular antibody-drug conjugates (ADCs), are a fast-growing area in research and in the pharmaceutical industry. The covalent attachment of an antibody to a chemical moiety can be an effective measure for drug targeting or can also positively impact pharmacokinetics of small molecular compounds by serum half-life extension. Stability, physicochemical properties, and degradation pathways of biotherapeutics or small molecule therapeutics are often not totally known and understood. However, ADCs represent a hybrid of small molecular and macromolecular components, and their properties are still not fully understood and described. This review discusses the alteration of the physicochemical properties of antibodies upon conjugation of chemical moieties to its surface and the resulting impact on ADC stability.

Keywords: antibody-drug conjugate(s) (ADC); conjugation; protein aggregation; protein structure; self-association; stability.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / metabolism
  • Chemical Phenomena*
  • Colloids / chemistry*
  • Colloids / metabolism
  • Drug Stability
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Immunoconjugates / chemistry*
  • Immunoconjugates / metabolism
  • Protein Aggregates / physiology*
  • Protein Binding / physiology

Substances

  • Antibodies, Monoclonal
  • Colloids
  • Immunoconjugates
  • Protein Aggregates