Severing Ties: Quantifying the Payload Release from Antibody Drug Conjugates
1Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Cell Chemical Biology
|January 18, 2020
Summary
Researchers developed novel fluorescence-based linkers to measure how quickly bonds break inside cells. This helps track antibody drug conjugate (ADC) kinetics for designing more effective cancer therapies.
Area of Science:
- Bioconjugation Chemistry
- Pharmacology
- Cell Biology
Background:
- Antibody drug conjugates (ADCs) are vital cancer therapeutics.
- The linker is crucial for ADC efficacy and toxicity, influencing cellular distribution and payload release.
- Quantifying linker behavior in real-time is essential for ADC design.
Purpose of the Study:
- To develop novel fluorescence-based linkers for ADCs.
- To quantify the rate of intracellular bond cleavage.
- To track live-cell kinetics of payload release for improved ADC design.
Main Methods:
- Creation of novel fluorescence-based linker systems.
- Utilizing fluorescence to monitor bond cleavage kinetics in live cells.
- Live-cell imaging and kinetic analysis of linker behavior.
Main Results:
- Successfully developed and implemented fluorescence-based linkers.
- Enabled quantification of intracellular bond cleavage rates.
- Provided real-time tracking of ADC linker kinetics within live cells.
Conclusions:
- Fluorescence-based linkers offer a powerful tool for studying ADC intracellular dynamics.
- Understanding linker kinetics is key to optimizing ADC design for enhanced efficacy and reduced toxicity.
- This approach facilitates the development of next-generation antibody drug conjugates.
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