Related Experiment Video

Updated: May 23, 2025

Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms
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Determination of High-affinity Antibody-antigen Binding Kinetics Using Four Biosensor Platforms

Published on: April 17, 2017

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Elucidating Critical Factors of Internalization and Drug Release of Antibody-Drug Conjugates (ADCs) Using Kinetic

Stanley Sweeney-Lasch1, Marie Quillmann2, Jens Hannewald1

  • 1Department of Discovery & Development Technologies, The Healthcare Business of Merck KGaA, Darmstadt 64293, Germany.

Bioconjugate Chemistry
|May 6, 2025
PubMed

Insights

A new tool, TORCH (Turn On after Release by CatHepsins), tracks antibody-drug conjugate (ADC) internalization and drug release. It reveals that receptor density, not antibody type, dictates payload release, aiding ADC cancer therapy development.

Area of Science:

  • Oncology
  • Biochemistry
  • Drug Delivery

Background:

  • Antibody-drug conjugates (ADCs) are a significant advancement in cancer therapy, with 15 approved agents.
  • ADCs deliver cytotoxic drugs specifically to tumor cells via antibody targeting.
  • Key to ADC efficacy are binding, cellular internalization, and subsequent drug release.

Purpose of the Study:

  • To introduce TORCH (Turn On after Release by CatHepsins), a novel molecule for assessing ADC internalization and drug release.
  • To investigate the relationship between receptor density and intracellular payload release in ADCs.

Main Methods:

  • Development of the TORCH molecule, featuring a fluorescence quencher system and a cathepsin B-cleavable linker.
  • Conjugation of the TORCH molecule to antibodies for tracking ADC behavior.
  • Analysis of ADC internalization and payload release across different antibodies and cell lines.

Main Results:

  • The TORCH molecule provides insights into ADC internalization and drug release dynamics.
  • Intracellular payload release was found to be directly proportional to receptor density.
  • Internalization efficiency per receptor was consistent across various antibodies and cell lines.

Conclusions:

  • TORCH is a valuable tool for evaluating ADC performance.
  • Receptor density is a primary determinant of ADC payload release, simplifying the understanding of ADC mechanisms.
  • Findings support the optimization of ADC design and application in cancer treatment.

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