Introduction to Antibody–Drug Conjugates

In the fight against cancer, antibody–drug conjugates (ADCs) form a versatile class of chemotherapeutic agents by combining the exquisite binding affinity and selectivity of a monoclonal antibody with the high cell-killing potential of a cytotoxic payload. Although the concept was originally postulated more than 60 years ago, only in the past ten years have ADCs started to firmly establish themselves in the field of targeted cancer therapy, with currently ten approved drugs and many more (>80) in the clinical pipeline. This chapter is an introduction to antibody–drug conjugates in the broad sense, starting with a historical perspective of the development of ADC technologies, to be followed by an overview of marketed and clinically most advanced ADCs. Next, the essential considerations to design and develop a successful ADC are separately highlighted: the target; the antibody and the (cytotoxic) payload;a quick overview of conjugation chemistries to attach the payload to the antibody;and of course, the linker, the essential part in the middle.