Pharmacokinetic Considerations for Antibody-Drug Conjugates against Cancer

Paul Malik, Colin Phipps, Andrea Edginton, Jonathan Blay

Research output: Contribution to journalReview articlepeer-review

37 Citations (Scopus)

Abstract

Antibody-drug conjugates (ADCs) are ushering in the next era of targeted therapy against cancer. An ADC for cancer therapy consists of a potent cytotoxic payload that is attached to a tumour-targeted antibody by a chemical linker, usually with an average drug-to-antibody ratio (DAR) of 3.5–4. The theory is to deliver potent cytotoxic payloads directly to tumour cells while sparing healthy cells. However, practical application has proven to be more difficult. At present there are only two ADCs approved for clinical use. Nevertheless, in the last decade there has been an explosion of options for ADC engineering to optimize target selection, Fc receptor interactions, linker, payload and more. Evaluation of these strategies requires an understanding of the mechanistic underpinnings of ADC pharmacokinetics. Development of ADCs for use in cancer further requires an understanding of tumour properties and kinetics within the tumour environment, and how the presence of cancer as a disease will impact distribution and elimination. Key pharmacokinetic considerations for the successful design and clinical application of ADCs in oncology are explored in this review, with a focus on the mechanistic determinants of distribution and elimination.

Original languageEnglish
Pages (from-to)2579-2595
Number of pages17
JournalPharmaceutical Research
Volume34
Issue number12
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.

ASJC Scopus Subject Areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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