ABSTRACT
Abstract .................................................................................................................. 325 Introduction ............................................................................................................ 326 Optimization of ADC Drug and Linker Components ............................................ 326
Conventional Drugs ........................................................................................... 326 Highly Potent Drugs .......................................................................................... 328 Linker Technology ............................................................................................ 330
Optimization of Conjugation Technology .............................................................. 334 Methods for Drug Attachment .......................................................................... 334 Drug to Antibody Ratios ................................................................................... 334 Engineered mAbs for Drug Attachment ............................................................ 335
ADCs in the Clinic ................................................................................................. 335 Conclusion ............................................................................................................. 337 References .............................................................................................................. 337
mAb carriers, the incorporation of highly potent drugs and novel conditionally stable linker technologies, and new conjugation technologies that minimally perturb the biologic characteristics of the mAb carrier and lead to well-characterized ADCs that can be manufactured reproducibly in high yields. Progress in this eld has been signicant, as evidenced from the pronounced clinical activities of SGN-35, an ADC directed against the CD30-positive malignancies, such as Hodgkin’s disease and anaplastic large cell lymphoma, and trastuzumab-DM1 which has shown activity in metastatic breast carcinoma. This review details many of the technological advancements made and provides examples of promising ADCs that are progressing in clinical development.
