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Case Study: An Antibody–Drug Conjugate Targeting MUC16 for Ovarian Cancer

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Antibody-Drug Conjugates and Immunotoxins

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

Abstract

Tumors can arise from healthy tissues due to dysregulation of key cellular pathways and abnormal responses to extracellular cues. The cells that comprise a malignant tumor bear molecular signatures that can either betray their tissue of origin or result from their abnormal physiology. Specifically, tumor cells express surface antigens that may be virtually absent from, or have a restricted distribution in, normal tissues. Expression of some of these surface antigens, notably growth factor receptors such as Met, IGF-1R, VEGF-R, and the ErbB/Her family, may provide a growth or survival advantage to the tumor cells [1]. For other antigens, the reason for their selective expression by tumors is much less clear. In either case, the surface antigen may represent a molecular address for targeting tumor cells with antibodies (a “tumor antigen”). A therapeutic strategy based on this concept uses antibodies conjugated to cytotoxic agents to deliver the agents selectively to the tumor cells and spare the normal tissues [2, 3]. This chapter will describe the preclinical development strategies, including target validation, in vitro characterization, and linker-drug impact on in vivo pharmacology and safety considerations of antibody–drug conjugates (ADC) targeting the ovarian cancer surface antigen, MUC16.

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Authors and Affiliations

  1. Department of Pharmacokinetics and Pharmacodynamics, Genentech, Inc., South San Francisco, CA, 94080, USA

    Douglas Leipold

  2. Department of Oncology Biologics, Novartis Institutes of BioMedical Research, Emeryville, CA, 94608, USA

    William G. Mallet

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  1. Douglas Leipold
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  2. William G. Mallet
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Correspondence to Douglas Leipold .

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  1. DNA Way 1, South San Francisco, 94080, California, USA

    Gail Lewis Phillips

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Leipold, D., Mallet, W.G. (2013). Case Study: An Antibody–Drug Conjugate Targeting MUC16 for Ovarian Cancer. In: Phillips, G. (eds) Antibody-Drug Conjugates and Immunotoxins. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5456-4_13

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  • DOI: https://doi.org/10.1007/978-1-4614-5456-4_13

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