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Issue 5, 2016
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Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry

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Abstract

Systemic chemotherapy, the current standard of care for the treatment of cancer, is rarely curative and is often accompanied by debilitating side effects. Targeted drug delivery stands as an alternative to chemotherapy, with the potential to improve upon its low efficacy and systemic toxicity. Among targeted therapeutic options, antibody–drug conjugates (ADCs) have emerged as the most promising. These conjugates represent a new class of biopharmaceuticals that selectively deliver potent cytotoxic drugs to cancer cells, sparing healthy tissue throughout the body. Despite this promise, early heterogenous ADCs suffered from stability, pharmacokinetic, and efficacy issues that hindered clinical development. Recent advances in antibody engineering, linkers for drug-release, and chemical site-selective antibody conjugation have led to the creation of homogenous ADCs that have proven to be more efficacious than their heterogeneous predecessors both in vitro and in vivo. In this minireview, we focus on and discuss recent advances in chemical site-selective modification strategies for the conjugation of drugs to antibodies and the resulting potential for the development of a new generation of homogenous ADCs.

Graphical abstract: Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry

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Publication details

The article was received on 13 jan. 2016, accepted on 10 feb. 2016 and first published on 12 feb. 2016


Article type: Minireview
DOI: 10.1039/C6SC00170J
Citation: Chem. Sci., 2016,7, 2954-2963
  • Open access: Creative Commons BY license
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    Construction of homogeneous antibody–drug conjugates using site-selective protein chemistry

    P. Akkapeddi, S. Azizi, A. M. Freedy, P. M. S. D. Cal, P. M. P. Gois and G. J. L. Bernardes, Chem. Sci., 2016, 7, 2954
    DOI: 10.1039/C6SC00170J

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