Recent advances in the construction of antibody–drug conjugates

  • A Corrigendum to this article was published on 19 February 2016

Abstract

Antibody–drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

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Figure 1: General structure of an immunoglobulin G1 (IgG1) highlighting key components.
Figure 2: General scheme highlighting typical methods for the construction of ADCs based on engineered antibodies.
Figure 3: General scheme highlighting typical methods for the construction of ADCs based on native antibodies.

Change history

  • 25 January 2016

    In the originally published version of this Perspective article, reference 42 contained an incorrect article number. The reference should have read 'Maruani, A. et al. A plug-and-play approach to antibody-based therapeutics via a chemoselective dual click strategy. Nature Commun. 6, 6645 (2015).' This has been corrected in all online versions.

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Acknowledgements

We are grateful to UCL, UCLB, NIHR BRC, MRC, BBSRC and EPSRC for support of our work in this area.

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Correspondence to Vijay Chudasama or Stephen Caddick.

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V.C. and S.C. are co-founders and directors of the company ThioLogics.

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Chudasama, V., Maruani, A. & Caddick, S. Recent advances in the construction of antibody–drug conjugates. Nature Chem 8, 114–119 (2016). https://doi.org/10.1038/nchem.2415

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