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Ado-Trastuzumab Emtansine

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Book cover Antibody-Drug Conjugates

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 17))

Abstract

Ado-trastuzumab emtansine (T-DM1 or KadcylaTM) is an antibody–drug conjugate (ADC) designed to deliver the antimitotic mertansine (DM1) drug to epithelial cancer cells overexpressing the oncoprotein HER2. T-DM1 has been approved in many countries for HER2-positive metastatic breast cancer (MBC) patients and has recently entered a phase 3 clinical trial for advanced HER2-positive gastric cancer patients. The success of T-DM1 lies in the optimization of drug delivery to the targeted cells by the antibody, while the nonreducible thioether bonds holding DM1 molecules to the antibody increase tolerability by preventing systemic release of DM1 molecules. When internalized by the targeted cell, DM1 molecules are activated and bind to tubulins, thereby inhibiting cell proliferation. Cytotoxicity of T-DM1 also arises upon binding of trastuzumab to HER2 by promoting antibody-dependent cell-mediated cytotoxicity and inhibiting HER2-dependent signaling pathways.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA

    Yun Luo & Sunil Prabhu

  2. Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA

    Jérôme J. Lacroix

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  1. Yun Luo
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  2. Jérôme J. Lacroix
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  3. Sunil Prabhu
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Correspondence to Yun Luo .

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Editors and Affiliations

  1. Western University of Health Sciences, Department of Pharmaceutical Sciences, Pomona, California, USA

    Jeffrey Wang

  2. University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, California, USA

    Wei-Chiang Shen

  3. University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, California, USA

    Jennica L. Zaro

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Luo, Y., Lacroix, J., Prabhu, S. (2015). Ado-Trastuzumab Emtansine. In: Wang, J., Shen, WC., Zaro, J. (eds) Antibody-Drug Conjugates. AAPS Advances in the Pharmaceutical Sciences Series, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-13081-1_12

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