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Antibody–Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments

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Abstract

Antibody–drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin’s lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several other agents are in advanced stages of clinical development, including sacituzumab govitecan for breast cancer, mirvetuximab soravtansine for ovarian cancer, rovalpituzumab tesirine for lung cancer, depatuxizumab mafodotin for glioblastoma, and oportuzumab monatox for bladder cancer. This review provides an overview of the recent clinical experience with the approved, most advanced, and other promising candidates of ADCs for solid tumors, including a description of biology and chemistry of ADCs, drug resistance and biomarkers, and the future perspective on combination strategies with these new immunoconjugates.

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  1. Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House 304, 10 North Grove St., Boston, MA, 02114, USA

    Aiko Nagayama, Leif W. Ellisen, Bruce Chabner & Aditya Bardia

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A. Bardia was supported by the US National Institutes of Health (NIH) (K12CA087723–14).

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Aiko Nagayama owns stock options in Chugai, Inc., and a family member has a leadership position with Chugai, Inc. and Roche, Inc. Bruce Chabner owns stocks in Seattle Genetics. Aditya Bardia has received consulting fees or honorarium by Genentech, Pfizer, and Novartis. Leif Ellisen declares no conflict of interest.

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Nagayama, A., Ellisen, L.W., Chabner, B. et al. Antibody–Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments. Targ Oncol 12, 719–739 (2017). https://doi.org/10.1007/s11523-017-0535-0

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