Introduction to Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are innovative biopharmaceutical products in which a monoclonal antibody is linked to a small molecule drug with a stable linker. Most of the ADCs developed so far are for treating cancer, but there is enormous potential for using ADCs to treat other diseases. Currently, ten ADCs have been approved by the United States Food and Drug Administration (FDA), and more than 90 ADCs are under worldwide clinical development. Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Tremendous strides have been made in antibody discovery, protein bioengineering, formulation, and delivery devices. This manuscript provides an overview of the biology, chemistry, and biophysical properties of each component of ADC design. This review summarizes the advances and challenges in the field to date, with an emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, drug-antibody ratio (DAR), and product development. The review emphasizes the lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications. The review discusses resistance mechanisms to ADCs, and give an opinion on future perspectives.