Antibody drug conjugates have not yet lived up to their potential, but there is hope – if we turn to the right solutions and techniques.
Charlie Johnson |
Antibody drug conjugates (ADCs) have garnered much attention in the industry because of their combination of high selectivity and high potency. However, few have been approved and they remain incredibly challenging to develop and manufacture, not least because of the significant challenges involved in combining the right cytotoxic payload at the optimal sites on the antibody in the most efficient way. These challenges are becoming more acute because of the increasing number of best-in-class ADCs that incorporate inherently hydrophobic DNA-interfering payloads, such as pyrrolobenzodiazepines or duocarmycin payloads. DNA-interfering agents are of high interest to ADC developers because they do not rely on a specific part of the cell cycle, unlike other payloads used in ADCs, such as tubulin inhibitors (for example, auristatins and maytansines). Though the payload only constitutes two percent of the overall ADC composition, it can dramatically increase the propensity of the ADC to aggregate.
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