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

Chapter
Part of the Cancer Drug Discovery and Development book series (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.

Keywords

Permeability Toxicity Agar Adenocarcinoma Polypeptide 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Pharmacokinetics and PharmacodynamicsGenentech, Inc.South San FranciscoUSA
  2. 2.Department of Oncology BiologicsNovartis Institutes of BioMedical ResearchEmeryvilleUSA

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