Optimizing and Intensifying ADC Aggregate Removal: A DoE Approach to Membrane Chromatography and Rapid Cycling

摘要

Antibody-drug conjugates (ADCs) represent a growing therapeutic segment of the oncology field. Five such treatments received market approval from the US Food and Drug Administration (FDA) between 2008 and 2018, whereas three were approved in 2019 andtwo each were approved in 2020 and 2021 (i).This disruptive technology combines highly potent small-molecule payloads with monoclonal antibodies (MAbs) to improve their specificity as cancer treatment. The antibodies deliver those toxic compounds directly to cancer cells but not to healthy cells, thereby mitigating many of the adverse effects associated with traditional chemotherapy. Once a MAb has bound to its target epitope on a tumor cell, it is internalized to merge with a lysosome inside the cell.Degradation of the resulting ADC-receptor complex releases the cytotoxin into the cell and causes apoptosis through a number of pathways (e.g., microtubule disruption and DNA damage).