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Selecting an Optimal Antibody for Antibody- Drug Conjugate Therapy

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Antibody-Drug Conjugates

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

Abstract

Antibody–drug conjugates (ADCs) represent an increasing proportion of therapeutics in preclinical and clinical development for the treatment of oncology indications. ADC-based therapies are attractive due to their potential to increase efficacy and reduce the systemic toxicity produced by other conventional anticancer regimens. ADCs are complex molecules, however, and their clinical success depends both on properties of the target in the context of disease and properties of the ADC itself—the antibody, the toxin payload, and the linker to which it is coupled, and the site and chemistry of linkage. In this chapter, we review some of the strategies that can be utilized to generate and characterize optimal ADC antibodies including the selection of appropriate targets, the development of tools for antibody generation and screening, approaches to antibody isolation, advanced screening strategies for lead antibody selection, antibody engineering to increase selectivity and potency, and selection of appropriate combinations of linker, payload, and linker attachment strategy.

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Authors and Affiliations

  1. Bioconjugates Discovery and Development, Pfizer, Pearl River, NY, USA

    Michael Ritchie & Puja Sapra

  2. Global Biotherapeutic Technologies, Pfizer, Cambridge, MA, USA

    Laird Bloom & Gregory Carven

Authors
  1. Michael Ritchie
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  2. Laird Bloom
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  3. Gregory Carven
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  4. Puja Sapra
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Correspondence to Puja Sapra .

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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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© 2015 American Association of Pharmaceutical Scientists

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Ritchie, M., Bloom, L., Carven, G., Sapra, P. (2015). Selecting an Optimal Antibody for Antibody- Drug Conjugate Therapy. 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_3

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