Antibody-drug conjugates (ADCs) represent a rapidly growing class of anti-cancer therapeutics in which a potent small molecule is linked to a monoclonal antibody.
To-date, two antibody-drug conjugates have been approved by regulators in the United States, Canada and Europe. These two modalities conjugate the cytotoxic drugs to either lysine or cysteine after reduction of four inter-chain disulfide bonds.
Due to the (1) small molecule property, the (1) chemical linking chemistry and (3) different amino acid conjugation, antibody-drug conjugates or ADCs exhibits a more complex and heterogeneous structure than the parent monoclonal antibody.
This complexity and heterogeneity present a significant challenge.
However, analytical characterization plays a crucial role during discovery, process scale-up, manufacturing, and release/stability testing of antibody-drug conjugates. This includes the determination of drug-to-antibody ratios (DAR) and sites of conjugation.
Hence, the selection of appropriate analytical techniques, which depends on the properties of the linker, the drug and the choice of attachment site, is critical.
This educational video addresses available solutions.
Video: Antibody Drug Conjugates (ADCs): Characterization Courtesy: © 2015 Waters Inc. Used with permission.