Antibody–drug conjugates: prospects for the next generation

The concept of a 'magic bullet' was first introduced by Paul Ehrlich in the early 1900s, he foresaw the advent of targeted therapies and the specific killing of harmful cells and/or microorganisms. However, these therapies were only used in the clinic after the second half of the 20th century with the development of specific monoclonal antibodies. To date, 13 antibody-drug conjugates (ADCs) are commercially available. Many advances have been made by modifying one or several of the three main components of an ADC, namely the antibody, the cleavable or non-cleavable linker or the payload, and by integrating conjugation chemistry. Despite these efforts, some problems have emerged and thus limit their effectiveness. New strategies could overcome these problems and identify the next generation of ADC.