Targeting cancer with antibody-drug conjugates: Promises and challenges

Antibody-drug conjugates (ADCs) are a rapidly expanding class of biotherapeutics that utilize antibodies to selectively deliver cytotoxic drugs to the tumor site. As of May 2021, the U.S. Food and Drug Administration (FDA) has approved ten ADCs, namely Adcetris®, Kadcyla®, Besponsa®, Mylotarg®, Polivy®, Padcev®, Enhertu®, Trodelvy®, Blenrep®, and Zynlonta™ as monotherapy or combinational therapy for breast cancer, urothelial cancer, myeloma, acute leukemia, and lymphoma. In addition, over 80 investigational ADCs are currently being evaluated in approximately 150 active clinical trials. Despite the growing interest in ADCs, challenges remain to expand their therapeutic index (with greater efficacy and less toxicity). Recent advances in the manufacturing technology for the antibody, payload, and linker combined with new bioconjugation platforms and state-of-the-art analytical techniques are helping to shape the future development of ADCs. This review highlights the current status of marketed ADCs and those under clinical investigation with a focus on translational strategies to improve product quality, safety, and efficacy.