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Cellular Trafficking of Monoclonal and Bispecific Antibodies

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Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

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Abstract

Monoclonal antibodies, including bispecific antibodies, represent versatile platforms for protein drug development. They have been successfully utilized for broad applications including agonizing or antagonizing cell surface receptors, bridging immune effector cells with cancer cells, and facilitating cell specific uptake of antibody–drug or antibody–oligonucleotide conjugates. Understanding the fate of antibodies and bispecific antibodies after binding their cell surface target(s) is of critical importance to drug development and pharmacology. Numerous publications have reported methods to assess antibody cell binding, internalization, intracellular trafficking, and the fate of the molecules. These methods can provide qualitative assessments for screening drug candidates, or quantitative assessments which can be used to inform mathematical models of cellular kinetics and drug disposition. Here, we focus on assays which offer quantitative assessments of the kinetics of antibody internalization, intracellular trafficking, and degradation or recycling. Experimental design, practical considerations for conducting experiments, and interpretation of results are considered.

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Authors and Affiliations

  1. Fusion Pharmaceuticals, Boston, MA, USA

    John J. Rhoden

  2. Biologics Investigational ADME, Eli Lilly and Company, Indianapolis, IN, USA

    Christopher M. Wiethoff

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  1. John J. Rhoden
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  2. Christopher M. Wiethoff
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Correspondence to John J. Rhoden .

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Editors and Affiliations

  1. College of Pharmacy, University of Michigan, Ann Arbor, MI, USA

    Gus R. Rosania

  2. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Greg M. Thurber

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Rhoden, J.J., Wiethoff, C.M. (2021). Cellular Trafficking of Monoclonal and Bispecific Antibodies. In: Rosania, G.R., Thurber, G.M. (eds) Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1250-7_12

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  • DOI: https://doi.org/10.1007/978-1-0716-1250-7_12

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  • Online ISBN: 978-1-0716-1250-7

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