Lactone Stabilization is Not a Necessary Feature for Antibody Conjugates of Camptothecins

Camptothecins exist in a pH-dependent equilibrium between the active, closed lactone and the inactive open-carboxylate forms. Several previous reports underscore the need for lactone stabilization in generating improved camptothecins, and indeed, such designs have been incorporated into antibody–drug conjugates containing this drug. Here, we demonstrate that lactone stabilization is not necessary for camptothecin-based ADC efficacy. We...