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Review
. 2016 Mar;37(2):66-74.
doi: 10.1002/bdd.1957. Epub 2015 Jun 8.

Challenges and advances in the assessment of the disposition of antibody-drug conjugates

Amrita V Kamath  1 , Suhasini Iyer  1
Affiliations
Review

Challenges and advances in the assessment of the disposition of antibody-drug conjugates

Amrita V Kamath et al. Biopharm Drug Dispos. 2016 Mar.

Abstract

Antibody-drug conjugates (ADCs) are a rapidly growing therapeutic platform for the treatment of cancer. ADCs consist of a cytotoxic small molecule drug linked to an antibody to provide targeted delivery of the cytotoxic agent to the tumor. Understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of ADCs is crucial in their design to optimize dose and regimen, to maximize efficacy and to minimize toxicity in patients. Significant progress has been made in recent years in this area, however, many fundamental questions still remain. This review discusses factors to consider while assessing the disposition of ADCs, and the unique challenges associated with these therapeutics. Current tools that are available and strategies to enable appropriate assessment are also discussed.

Keywords: antibody drug conjugate; biotherapeutics; cancer; pharmacokinetics; preclinical.

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Figures

Figure 1
Figure 1
Proposed mechanism of ADC disposition. Upon binding to its target antigen on tumor cell, the ADC is internalized via receptor‐mediated endocytosis and trafficked from the endosome to the lysosome. The cytotoxic drug is released from the ADC by either deconjugation or catabolism in these intracellular compartments. The released cytotoxic drug then binds to its target and causes cell death
Figure 2
Figure 2
Typical pharmacokinetic profiles of commonly measured ADC analytes. Total antibody which measures both conjugated and naked antibody; conjugated antibody which measures antibody that has at least one drug attached to it; antibody‐conjugated drug which measures any drug still conjugated to the antibody; unconjugated drug which measures drug that is not associated with the antibody
See this image and copyright information in PMC

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