The AAPS Journal

, Volume 17, Issue 2, pp 339–351

Antibody Drug Conjugates: Design and Selection of Linker, Payload and Conjugation Chemistry

Review Article Theme: Critical Considerations for Design and Development of Antibody Drug Conjugates
Part of the following topical collections:
  1. Theme: Critical Considerations for Design and Development of Antibody Drug Conjugates

Abstract

Antibody drug conjugates (ADCs) have emerged as an important pharmaceutical class of drugs designed to harness the specificity of antibodies with the potency of small molecule therapeutics. The three main components of ADCs are the antibody, the linker, and the payload; the majority of early work focused intensely on improving the functionality of these pieces. Recently, considerable attention has been focused on developing methods to control the site and number of linker/drug conjugated to the antibody, with the aim of producing more homogenous ADCs. In this article, we review popular conjugation methods and highlight recent approaches including “click” conjugation and enzymatic ligation. We discuss current linker technology, contrasting the characteristics of cleavable and non-cleavable linkers, and summarize the essential properties of ADC payload, centering on chemotherapeutics. In addition, we report on the progress in characterizing to determine physicochemical properties and on advances in purifying to obtain homogenous products. Establishing a set of selection and analytical criteria will facilitate the translation of novel ADCs and ensure the production of effective biosimilars.

KEY WORDS

ADC antibody drug conjugate biopharmaceutics enzymatic ligation therapeutics 

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Copyright information

© American Association of Pharmaceutical Scientists 2015

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Pharmaceutical ChemistryUniversity of UtahSalt Lake CityUSA

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