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Assay Methodologies and Challenges

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Antibody-Drug Conjugates and Immunotoxins

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

Abstract

Accurate characterization of antibody–drug conjugates (ADCs) is critical for development of an efficacious and safe therapeutic. Each component of an ADC, the antibody, linker, and drug, is important to achieve efficacy with minimal toxicity. The ability to detect, characterize, and quantify this multicomponent entity is critical for their successful optimization and development. Especially important is the ability to quantify ADCs in biological matrices such as serum or plasma. However, the design of reliable and accurate analytical and bioanalytical methods is complicated by the heterogeneity of ADCs. This chapter describes some of the general methods for characterization and quantitation of ADCs and highlights the particular assay challenges associated with these complex molecules.

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Abbreviations

ADC:

Antibody–drug conjugate

ADCC:

Antibody-dependent cell-mediated cytotoxicity

CDC:

Complement-dependent cytotoxicity

DAR:

Drug-to-antibody ratio

ELISA:

Enzyme-linked immunosorbent assay

HIC:

Hydrophobic interaction chromatography

MALDI:

Matrix-assisted laser desorption/ionization

MS:

Mass spectrometry

RP-HPLC:

Reversed-phase high-pressure liquid chromatography

TOF:

Time of flight

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Acknowledgements 

We thank Cris Lewis, Hicham Alaoui, and Ola Saad for their useful comments on the manuscript.

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Authors and Affiliations

  1. Department of Biochemical and Cellular Pharmacology, Genentech, Inc., MS#98, 1 DNA Way, South San Francisco, CA, 94080, USA

    Katherine R. Kozak

  2. Department of Protein Chemistry, Genentech, Inc., MS#63, 1 DNA Way, South San Francisco, CA, 94080, USA

    Helga Raab

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  1. Katherine R. Kozak
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Correspondence to Katherine R. Kozak .

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

    Gail Lewis Phillips

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Kozak, K.R., Raab, H. (2013). Assay Methodologies and Challenges. 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_3

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  • DOI: https://doi.org/10.1007/978-1-4614-5456-4_3

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