Therapeutic antibody-drug conjugates or ADCs combine a target specific monoclonal antibody or mAb with the cell-killing activity of a small molecule drug and deliver the combined agent directly to specifically targeted cancer cells. Compared with traditional small-molecule chemotherapy, antibody-drug conjugates limit the risk of cytotoxicity to non-cancerous cells. At the same time, ADCs enable the use of more potent cytotoxic agents.
Over the last decade, several promising modalities have been developed that follow the same basic principles of antibody-drug conjugate based therapies but employ unique cytotoxic agents and conjugation strategies designed to realize therapeutic benefit. These new drugs may offer valuable options for patients suffering from some of the most serious blood related diseases as well as many forms of cancer. ADCs are among the fastest growing segment of biologics.
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.
The production of antibody-drug conjugates relies on the chemical conjugation. The complexity and heterogeneity of antibody-drug conjugates present a challenge to some of the conventional analytical methods of analysis the live science industry has relied on for (standard) biologics characterization.
In a just accepted manuscript published in December 4, 2014 online edition of Molecular Pharmaceutics, a journal published by the American Chemical Society, John Fay Valliere-Douglass, Shawna Mae Hengel and Lucy Y. Pan at Seattle Genetics’ Analytical Sciences, in Bothel, WA, USA, review some of the more recent methodological approaches in mass spectrometry that have bridged the gap that is created when conventional analytical techniques provide an incomplete picture of the product quality of antibody-drug conjugates.
In their review, the authors of the article specifically address mass spectrometric approaches that preserve and/or capture information about the native structure of antibody-drug conjugates and provide unique insights into the higher-order structure (HOS) of these therapeutic molecules.