Antibody Conjugation Technologies

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.