Category: Automation and High-Throughput Technologies
Antibody–Drug Conjugates (ADCs) hold tremendous promise for the treatment of cancer, combining the efficacy of small molecule drugs with the targeting selectivity of antibodies, resulting in increased efficacy and decreased off target toxicity. This key technology based outcome has made ADCs one of the most highly investigated types of oncology therapeutic, with a market expected to exceed 10 billion dollars by 2021. The discovery path to an ADC encounters multiple technology challenges. A key step is creating diverse monoclonal antibody panels with sufficient affinity, stability and epitope diversity to support robust target validation workflows as direct drug conjugates. Because these characteristics cannot be predicted by primary sequence, it is important to screen multiple antibodies at the onset of any program. This, combined with the high failure rate of target validation efforts, justifies the investment of time and resources to create a throughput based production system. Finally, because of the constantly changing landscape of Oncology targeting, any attempt to automate the generation of drug candidates must be flexible enough to support a wide range of protein scaffold formats. Here we describe a workstation-based workflow to generate a large number of ADCs for target validation and discovery. Transient transfections of Expi293 mammalian cells are performed using a 35 mL Hamilton STAR Plus and supernatants are purified using a ProteinMaker. Purified eluate is re-arrayed into dialysis plates using a Hamilton STAR platform, and then buffer exchanged and concentrated using an Unchained Labs Freeslate Jr. This process provides 96-well plates of proteins to the chemistry group which then utilizes an in-house developed automation platform for rapid antibody drug conjugation and purification (RADCAP). An internal QC package consisting of SEC, endotoxin levels and Mass Spectrometry identity confirmation is produced using internally developed systems. Using this platform a single user is capable of producing, in a 2 week timeframe, up to 100 buffer exchanged, normalized proteins to support antibody discovery, protein engineering and ADC development.
Maria Cristina Harris– Scientist, Abbvie Bioresearch Center, Worcester, MA
Abbvie Bioresearch Center
Maria Harris is a Scientist in the Biologics Generation Group at Abbvie Bioresearch Center in Worcester, MA. She joined Abbott/Abbvie in 2006 and has been supporting biologics drug discovery projects in Oncology, Immunology and Neuroscience. Maria's scientific training is in Biochemistry. She received her MS at the Universita' dell'Insubria in Varese, Italy.