This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract Antibody–drug conjugates (ADC) are one of the fastest growing anticancer drugs. This approach comprises a mAb conjugated to the cytotoxic payload via a chemical linker that directed toward a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. ADCs are complex molecules that require careful attention to various components. Selection of an appropriate target, an mAb, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC, and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design. Moreover, this review also shed light on the current status of ADCs that have gained regulatory approval from the FDA including a description of biology and chemistry, metabolic profiles, adverse events, drug interactions, and the future perspective on combination strategies with other agents, including immunotherapy. Footnotes Mol Cancer Res 2020;18:3–19 Received June 2, 2019. Revision received August 22, 2019. Accepted October 22, 2019. Published first October 28, 2019. ©2019 American Association for Cancer Research. Log in using your username and password Username * Forgot your user name or password? Purchase access You may purchase access to this article. This will require you to create an account if you don't.
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