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Improving the Safety Profile of ADCs

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Innovations for Next-Generation Antibody-Drug Conjugates

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Antibody–drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver cytotoxic agents directly into tumor cells. The plethora of ADCs investigated in clinical trials in recent years has enabled characterization of the major challenges faced by this therapeutic modality. With regard to safety, non-target-mediated toxicities, which are independent of the targeted antigens and similar for ADCs with the same linker-payloads, often drive dose-limiting events in patients and at the same time question the targeting efficiency of current ADCs. Development-limiting target-mediated toxicities have only been reported for a few ADCs. This manuscript will provide an overview of the major clinically relevant toxicities of ADCs with a presentation of key ADC attributes influencing these toxicities and discussion of potential mechanisms. Current research efforts to mitigate ADC-associated toxicities, including among others site-specific conjugation chemistry and prevention of normal tissue binding, will be presented and could be critical to future ADC endeavors.

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Acknowledgements

All procedures performed on animals were conducted in accordance with regulations and established guidelines and were reviewed and approved by an Institutional Animal Care and Use Committee or through an ethical review process.

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Authors and Affiliations

  1. Pfizer Inc, Drug Safety Research and Development, Pearl River, NY, USA

    Magali Guffroy & Martin Finkelstein

  2. Preclinical Safety Oncology, AbbVie Stemcentrx LLC, South San Francisco, CA, USA

    Hadi Falahatpisheh

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  1. Magali Guffroy
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  2. Hadi Falahatpisheh
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  3. Martin Finkelstein
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Correspondence to Magali Guffroy .

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  1. Mersana Therapeutics, Inc., Cambridge, Massachusetts, USA

    Marc Damelin

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Guffroy, M., Falahatpisheh, H., Finkelstein, M. (2018). Improving the Safety Profile of ADCs. In: Damelin, M. (eds) Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78154-9_3

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  • DOI: https://doi.org/10.1007/978-3-319-78154-9_3

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