Antibody-drug conjugates: challenges, solutions and future potential
The ability to precisely direct powerful therapeutics not only makes treatments more effective, but also prevents debilitating side effects. Here, Dave Elder and Stacey Treichler highlight the great potential of antibody-drug conjugates (ADCs) for improved treatment of oncology indications and beyond.
TARGETED DRUG DELIVERY is the ability to accurately target molecules to their site of action, minimising unwanted side effects. In conventional chemotherapy, cytotoxic drugs are delivered orally or systemically, but their efficacy is often compromised by extensive side effects. In contrast, antibody-drug conjugates (ADCs) can deliver potent anti-cancer agents – that are often too toxic to be dosed systemically on their own – directly to cancer cells, thereby minimising unwanted systemic toxicity. ADCs, a type of bioconjugate/immunoconjugate, work by chemically linking the potent anti-cancer agent to a monoclonal antibody (mAb).1 Ideally, this chemical linker is stable to systemic metabolism, but cleavable within target cells such that it releases the cytotoxic agent selectively within the target cells, ie, after lysosomal degradation.2 The mAb also plays a part, selectively targeting specific surface antigens that are present on tumour cells. Ideally, the selected antigen target is only expressed by the diseased cells and shows limited expression in healthy cells.1
Adcetris (brentuximab vedotin), Besponsa, Blenrep (belantamab mafodotin-blmf), Enhertu (trastuzumab deruxtecan), Mylotarg, Opdivo (nivolumab), PADCEV, Polivy (polatuzumab vedotin), trastuzumab emtansine (Kadcyla), Trodelvy (sacituzumab govitecan-hziy)