Developments in the Use of Antibody-Drug Conjugates

With the recent approvals of brentuximab for the treatment of refractory Hodgkin lymphoma and ado-trastuzumab emtansine for relapsed metastatic HER2+ breast cancer, the hope for delivering targeted chemotherapy in the form of an antibody-drug conjugate (ADC) against many cancers is rapidly growing. The strategy of delivering a potent cytotoxic via a monoclonal antibody to a tumor has been made feasible by marked advances in the technology of formulating and manufacturing these ADCs. The development of stable linkers together with the identification of relevant biomarkers has been a key to the success of this class of agent. The possibilities for deploying this technology in the treatment of a wide range of solid cancers are limited only by the discovery of suitable targets, those which are highly expressed on cancer cells and not, or minimally, on normal tissues. That said, with the improved linker engineering, the ADC affords the best opportunity at shrinking tumors while minimizing side effects. A variety of ADCs are in clinical trials studying a number of different tumor types as diverse as small cell lung and renal cell cancer. A future of potent anticancer therapy with minimal toxicity appears closer to reality for our patients.