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Application of Cell-Based Assays in Clinical Trials

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Translating Molecular Biomarkers into Clinical Assays

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 21))

Abstract

Cell-based assays using primary cells and cell lines have been increasingly utilized to address scientific questions related to disease and therapeutic agents in clinical trials to: (1) gain greater understanding into the mechanism of action (MOA) of therapeutic agents; (2) identify patients that may respond to therapy; and (3) monitor pharmacodynamic biomarkers. Cell-based assays are also vital for the evaluation of target engagement or saturation, evaluation of safety markers, and monitoring mechanisms of resistance. However, implementation of cell-based assays in a clinical setting is challenging due to inherent variability (e.g., inter-subject, inter-assay) and stochastic factors that affect assay outcome. Hence, appropriate cell-based assay qualification and validation is required prior to testing clinical study samples. Assay qualification should include: (1) evaluation and optimization of relevant assay controls; (2) well-defined cell culture conditions; (3) stability determination of the analytes; and (4) inter-assay and intra-assay variance. This chapter provides an overview for some of the cell-based assays applicable for clinical studies. Examples of such assays include functional assays utilizing primary cells and cell lines, antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) assays, circulating tumor cell (CTC) assays, and receptor occupancy assays. Implementation and translational utility of these cell-based assays in clinical studies, including assay challenges and result interpretation, are discussed.

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Acknowledgments

The authors would like to thank Brett M. Hall, Senior Director Oncology Biomarkers, Janssen R&D for his review and suggestions. The authors would also like to thank the Diane Mohr, Director Biomarker Operations and Eric Dichter, Assistant General Counsel (all from Janssen R&D) for review and approval of the chapter.

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Authors and Affiliations

  1. Oncology Translational Research, Janssen Research and Development, Janssen Pharmaceutical Companies of Johnson and Johnson, LLC, 1400 McKean Road, Spring House, PA, USA

    Manjula P. Reddy & Amy Kate Sasser

Authors
  1. Manjula P. Reddy
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  2. Amy Kate Sasser
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Correspondence to Manjula P. Reddy .

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Editors and Affiliations

  1. Translational Biomarkers and Personalized Medicine, Edison, New Jersey, USA

    Russell Weiner

  2. MKelley Consulting LLC, West Chester, Pennsylvania, USA

    Marian Kelley

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© 2016 American Association of Pharmaceutical Scientists

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Reddy, M.P., Sasser, A.K. (2016). Application of Cell-Based Assays in Clinical Trials. In: Weiner, R., Kelley, M. (eds) Translating Molecular Biomarkers into Clinical Assays . AAPS Advances in the Pharmaceutical Sciences Series, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-40793-7_11

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