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Current Trends in the Clinical Development of Antibody-Drug Conjugates in Oncology

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Abstract

Antibody-drug conjugates (ADCs) belong to a class of drugs that combine the antigen specificity of monoclonal antibodies with the potent cell-killing abilities of cytotoxic compounds. Previous technical challenges in developing first- and second-generation ADCs are reflected by the small number of compounds that have achieved marketing authorisation. However, recent advances in antibody, linker and toxin technology have led to renewed interest in these pharmaceuticals, and many are now at various stages of clinical development. The cytotoxic agents predominantly used in ADCs fall into two categories: microtubule disrupting agents and DNA-damaging agents. Both classes of drugs have been used in cancer chemotherapy for many years as “naked” agents, with the well-known, on- and off-target side effects affecting healthy tissues. Conjugation to an antibody allows more targeted drug delivery enabling the use of more potent compounds, giving the conjugate a greater therapeutic window than the unconjugated toxin. This review discusses the successes and failures of ADCs and their conjugated cytotoxic agents and explores promising novel technologies for ADCs that have not yet been granted regulatory approval for commercialisation. Improving ADC therapeutics for the future will require effective antibody target selection, matching the cytotoxic drug to the target and indicated disease, and achieving a safety profile significantly better than current chemotherapy regimens.

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The authors thank Dr Francesca Zammarchi for critically reviewing this article.

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  1. Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Joseph Dott, Bams Abila & Jens U. Wuerthner

  2. ADC Therapeutics, Route de la Corniche 3B, 1066, Epalinges, Switzerland

    Jens U. Wuerthner

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Joseph Dott and Bams Abila declare that they have no conflict of interest. Jens Wuerthner is an employee ADC Therapeutics, a company developing PBD-based ADCs for different indications in oncology.

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Dott, J., Abila, B. & Wuerthner, J.U. Current Trends in the Clinical Development of Antibody-Drug Conjugates in Oncology. Pharm Med 32, 259–273 (2018). https://doi.org/10.1007/s40290-018-0238-6

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