Antibody Drug Conjugates (ADCs) use targeting ability of monoclonal antibodies to deliver
potent cytototoxic payloads to their intended target. The linker encompasses a conjugating functionality
suitable for attachment to the antibody, a spacer unit that typically incorporates a hydrophilic element
and a trigger which releases the potent cytototoxic warhead. Understanding the conflicting requirements
of ADC design, providing stability in systemic circulation but efficient payload release once the ADC
reaches its intended target, is crucial to effective linker development. ADC linker design has been approached
in a variety of different ways, with increasingly elegant solutions continuing to be reported as
understanding of the intricate design complexities increases. This review focuses on the synthetic approaches
used in ADC linkers, and the impact of linker design on antibody conjugation, ADC pharmacokinetics
and payload release. Linker approaches utilized in commercial ADCs as well as ADCs currently
in clinical, pre-clinical and early stage development are discussed.
Keywords: Antibody Drug Conjugate, Linker Design, Conjugation Technologies, Disulfide Rebridging, Release Mechanism,
Toxin Specific Linkers.
Rights & PermissionsPrintExport