Improving the Safety Profile of ADCs

  • Magali GuffroyEmail author
  • Hadi Falahatpisheh
  • Martin Finkelstein
Part of the Cancer Drug Discovery and Development book series (CDD&D)


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.


Toxicology Safety Toxicity Thrombocytopenia Neutropenia Off-target On-target Target Dependent Independent Liver Kidney Peripheral neuropathy Ocular Dose-limiting DLT Auristatin Microtubule inhibitor Calicheamicin Maximum tolerated dose MTD Therapeutic index 



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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Magali Guffroy
    • 1
    Email author
  • Hadi Falahatpisheh
    • 2
  • Martin Finkelstein
    • 1
  1. 1.Pfizer Inc, Drug Safety Research and DevelopmentPearl RiverUSA
  2. 2.Preclinical Safety Oncology, AbbVie Stemcentrx LLCSouth San FranciscoUSA

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