Related Experiment Video

Updated: Aug 6, 2026

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
08:47

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Published on: March 6, 2019

Linker Chemistry in Antibody-Drug Conjugates: Current Strategies, Clinical Pharmacokinetic Analyses, and Linker-Free

Theeraphop Prachyathipsakul1, Prachi Gupta1, Seth Thayumanavan2

  • 1Department of Chemistry, University of Massachusetts, Amherst, Massachusetts01003, United States.

Bioconjugate Chemistry
|July 23, 2026
PubMed

Insights

Antibody-drug conjugates (ADCs) utilize linker chemistry for targeted cancer therapy. Advancements in linker technology, from cleavable to linker-free designs, are improving drug delivery and patient outcomes.

Area of Science:

  • Oncology
  • Bioconjugation Chemistry
  • Pharmaceutical Sciences

Background:

  • Antibody-drug conjugates (ADCs) offer targeted cytotoxic payload delivery to cancer cells, aiming to minimize off-target effects compared to traditional chemotherapy.
  • Despite promising clinical successes, many ADCs in development face challenges, highlighting the critical role of linker technology.

Purpose of the Study:

  • To review and discuss various linker chemistries used in antibody-drug conjugate development.
  • To focus on advancements in antibody modification and linker cleavage strategies.
  • To correlate linker technologies with clinical pharmacokinetic outcomes and explore emerging linker-free approaches.

Main Methods:

  • Literature review and synthesis of existing data on ADC linker technologies.
  • Analysis of the evolution of linker chemistry from stochastic to site-specific modifications.
  • Correlation of linker properties with pharmacokinetic data from clinical studies.

Main Results:

  • Linker chemistry has evolved significantly, moving from non-stimuli-responsive to site-specifically modified cleavable linkers.
  • Specific linker technologies demonstrate varying pharmacokinetic profiles in clinical applications.
  • Emerging linker-free technologies show potential for more efficient antibody-conjugated delivery.

Conclusions:

  • Linker design is a critical determinant of ADC efficacy and safety.
  • Continued innovation in linker chemistry is essential for advancing ADC therapeutics.
  • Future directions include exploring linker-free conjugation for enhanced targeted delivery.

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