Recent progress in linker technology for antibody-drug conjugates: Methods for connection and release

Research output: Chapter in Book/Report/Conference proceedingChapter


Linkers connect antibodies to payloads in antibody-drug conjugates (ADCs). The choice of linker controls the conjugation-site and antibody-drug ratios as well as the releasing mechanism and the rate of release. In order to optimize the efficacy of ADCs, improvements in linker technology, especially site-selective conjugation methods, are being explored. Site-specific conjugation methods involving non-natural amino acid incorporation, glycan utilization, and enzymatic addition methodologies are discussed in this chapter. In addition to conjugation methodology, payload-releasing strategy is a very important consideration for delivering maximum focused toxicity to the vicinity of the tumor cells. Although protease-cathepsin-cleavable dipeptide Val-Cit sequence is currently the most common choice for an enzymatic cleavable linker, novel approaches for releasing payloads, such as light stimulation and chemical reaction, have been reported. In this chapter, advances in development of linker technology will be reviewed.

Original languageEnglish
Title of host publicationCancer Drug Delivery Systems Based on the Tumor Microenvironment
PublisherSpringer Japan
Number of pages31
ISBN (Electronic)9784431568803
ISBN (Print)9784431568780
Publication statusPublished - 2020 Jan 1
Externally publishedYes


  • 1,6-elimitation reaction
  • Anti-IL-7R antibody
  • Anti-insoluble fibrin (IF) antibody
  • Bio-orthogonal reaction
  • Cancer stromal targeting (CAST) therapy
  • Cathepsin
  • Diketopiperazine-releasing spacer
  • Drug-to-antibody ratio (DAR)
  • Endo-β-N-acetylglucosaminidase
  • Enhanced permeability and retention (EPR) effect
  • Formylglycine-generating enzyme
  • Galactosyl transferase
  • Glycan
  • Inverse-electron-demand Diels-Alder reaction
  • Linker
  • Maleimide
  • Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)
  • Monomethyl auristatin E (MMAE)
  • MS imaging
  • Nucleophilic aromatic substitution (SAr)
  • p-aminobenzyl carbamate
  • Plasmin
  • Polyethylene glycol (PEG)
  • Sialyl transferase
  • SN-38
  • Sortase A
  • Strain-promoted azide-alkyne cycloaddition reaction
  • Therapeutic index
  • Transglutaminase
  • Val-Cit
  • β-glucuronidase-cleavable linker

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Engineering(all)


Dive into the research topics of 'Recent progress in linker technology for antibody-drug conjugates: Methods for connection and release'. Together they form a unique fingerprint.

Cite this