Calicheamicins as Antibody–Drug Conjugate (ADC) Payloads
The calicheamicins are a class of naturally occurring DNA-damaging agents that were isolated and identified over 30 years ago. From the outset, it was recognized that the extreme cytotoxic potencies of members of this class of natural products precluded their use as stand-alone agents, but their potential utility as payloads for antibody–drug conjugates (ADCs) inspired researchers to search for the ideal calicheamicin derivative that could be successfully employed in this context. This chapter reviews the discovery of the calicheamicins and related compounds, the evolution of the so-called “AcBut-DMH–