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Review
. 2021 May 15;26(10):2943.
doi: 10.3390/molecules26102943.

Antibody-Drug Conjugates-A Tutorial Review

Stephanie Baah  1 , Mark Laws  1 , Khondaker Miraz Rahman  1
Affiliations
Review

Antibody-Drug Conjugates-A Tutorial Review

Stephanie Baah et al. Molecules. .

Abstract

Antibody-drug conjugates (ADCs) are a family of targeted therapeutic agents for the treatment of cancer. ADC development is a rapidly expanding field of research, with over 80 ADCs currently in clinical development and eleven ADCs (nine containing small-molecule payloads and two with biological toxins) approved for use by the FDA. Compared to traditional small-molecule approaches, ADCs offer enhanced targeting of cancer cells along with reduced toxic side effects, making them an attractive prospect in the field of oncology. To this end, this tutorial review aims to serve as a reference material for ADCs and give readers a comprehensive understanding of ADCs; it explores and explains each ADC component (monoclonal antibody, linker moiety and cytotoxic payload) individually, highlights several EMA- and FDA-approved ADCs by way of case studies and offers a brief future perspective on the field of ADC research.

Keywords: ADC; antibody–drug conjugate; cytotoxic payload; linker; monoclonal antibody; tutorial review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The evolution of ADC therapies. Figure redrawn based on the work of Perez et al. [7].
Figure 2
Figure 2
A general antibody structure (valency 2).
Figure 3
Figure 3
Structures of different linker groups used in ADCs. (a) A cleavable hydrazone linker and disulphide trigger as used in Mylotarg®; (b) an MC–Val–Cit–PABC linker, combining the non-cleavable MC and dipeptide cleavable Val–Cit linkers with a PABC spacer, as used in Adcetris®; (c) a non-cleavable MCC linker as used in Kadcyla®.
Figure 4
Figure 4
Structures of representative members of the various payload classes used in ADCs.
Figure 5
Figure 5
The structure of gemtuzumab ozogamicin (Mylotarg®, top) and trastuzumab emtansine (Kadcyla®, bottom).
See this image and copyright information in PMC

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