Streamlining Drug Development: Native LC-MS for Rapid Screening and Drug Product QC Release Testing of Antibody Drug Conjugates
With over 500 active clinical trials to date, antibody drug conjugates (ADC) have proven to be an increasingly important class of protein therapeutics for the treatment of cancer. ADCs combine the potency of cytotoxic agents and the specificity of antibodies that deliver drugs to the targeted tumor cells. Conjugation of maleimide-linker-drugs to the reduced thiols of inter-chain cysteine residues in antibodies results in a heterogeneous mixture of ADC non-covalent complexes with drugs ranging from 0-8. Therefore, it is important to develop reliable methods that can conserve the non-covalent complexes, unambiguously determine, and consistently monitor drug-to-antibody ratios (DAR) of ADCs.
In this webinar, we will present an LC-MS-based workflow performed in native conditions that can unambiguously provide drug load distribution and DAR values of two ADCs at different stages in the drug development process. The Bruker maXis II UHR qTOF coupled to a UPLC system with ammonium acetate buffer was used to optimize the conjugation process for ADC A while in drug discovery. This same workflow was pre-validated in preparation for QC release testing of ADC B, an early stage development ADC. After qualification, this Native LC-MS method will be used to report drug-load distribution and average DAR as part of the Control System of ADC B.
Speaker: Lieza M. Danan-Leon PhD., Senior Scientist, Stemcentrx
June 28, 2016
For further information on World ADC webinars and how you can get involved visit worldadc-webinars.com