Antibody Drug Conjugates: Preclinical Considerations

The AAPS Journal
Gadi G Bornstein

Abstract

The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.

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Citations

Aug 18, 2020·Medicinal Research Reviews·Xiaoxiao YangBinghe Wang
Aug 11, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brooke M Rock, Robert S Foti
Feb 23, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sharad SharmaDhaval K Shah
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Aug 21, 2021·Bioconjugate Chemistry·Christopher J AddonizioMatthew J Webber
Jul 3, 2019·ACS Central Science·Lei ZouMatthew J Webber

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