Chemical Linkers in Antibody–Drug Conjugates (ADCs)
Chapter 2: Antibody Conjugation Technologies
Published:15 Dec 2021
G. T. Hermanson and F. L. van Delft, in Chemical Linkers in Antibody–Drug Conjugates (ADCs), ed. F. van Delft and J. M. Lambert, The Royal Society of Chemistry, 2021, ch. 2, pp. 32-70.
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A key quality attribute of any ADC is the mode of attachment of the linker-drug to the monoclonal antibody. Early generation technologies were based exclusively on one of two approaches, i.e. covalent bond formation with – abundantly available – lysine or cysteine sidechains. However, the need to develop ADCs with increased therapeutic index, and the insight that homogeneity, proper site selection, and stability all play a key role in this matter, has served as an inspiration for the development of a contemporary conjugation toolbox filled with alternative conjugation approaches. This chapter discusses in depth the state of the art in antibody conjugation, providing a comprehensive overview of technologies currently employed in clinical and late-stage preclinical ADC programs. The pros and cons of each technology are also discussed. Besides, a range of promising emerging technologies is highlighted, judged on their potential for application in next-generation ADCs.