Current Flow Cytometry Methods for the Clinical Development of Immunomodulatory Biologics
Flow cytometry is a highly versatile single cell analysis technology enabling multiparametric immune monitoring during clinical development . Cell data collected on morphology, activation state, and effector function from specific immune cell populations
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Abstract Flow cytometry is a highly versatile single cell analysis technology enabling multiparametric immune monitoring during clinical development. Cell data collected on morphology, activation state, and effector function from specific immune cell populations can be measured simultaneously in peripheral blood and/or tissue to determine drug efficacy. As such, flow cytometric laboratory testing is increasingly in demand to meet biomarker requirements for novel immunomodulatory biologics (IMBs) being evaluated in early and late stage clinical trials. In the context of clinical trial design, flow cytometric biomarkers may be used to assess safety, target engagement, and pharmacodynamics to enable clinical decision making. Flow cytometric applications such as immunophenotyping of TBNK immune cells is commonly employed as a safety biomarker to assess potential drug related immunotoxicities. IMB target engagement and pharmacodynamic effects on immune cell distribution and/or effector function can be integrated with traditional pharmacokinetic results to yield useful information relevant to dose selection, dosing intervals in addition to informing on mechanism of action. In all cases, a fit-for-purpose analytical validation is applied to flow cytometric assays prior to their clinical implementation to ensure confidence in biomarker measurements, while CRO placement of these assays offers a significant degree of standardization during clinical sample analysis to ensure high biomarker data quality.
Disclosure Statement Richard Wnek is an employee of Merck & Co., Inc. and holds stock in the company. R. Wnek (&) Translational Molecular Biomarkers, Merck & Co., Inc., Rahway, USA e-mail: [email protected] M. Tseng Amerimmune Immunology Laboratory, O & O Alpan, LLC, Fairfax, VA 22030, USA e-mail: [email protected] D. Wu Oncology Translational Research, Janssen Research and Development, Spring House, USA e-mail: [email protected] © American Association of Pharmaceutical Scientists 2016 R. Weiner and M. Kelley (eds.), Translating Molecular Biomarkers into Clinical Assays, AAPS Advances in the Pharmaceutical Sciences Series 37, DOI 10.1007/978-3-319-40793-7_13
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Keywords Immunomodulatory biologic Biotherapeutic entities that target the activation or suppression of host immune responses as a means of disease treatment. Clinical development The clinical trials phase of drug development purposed with determining safety and efficacy of novel molecular entities. Flow cytometry Fluorescence based technology capable of simultaneously resolving phenotype and effector function of cells present in complex biological matrices. Immune monitoring Functional characterization and/or enumeration of immune cell subsets in peripheral blood and/or tissue.
Introduction Immunomodulatory biologics (IMBs) are biotherapeutic entities that enhance or suppress the host immune response as a means of treating various cancers and complex immune disorders. With their targeted selectivity and superior clinical efficacy, IMBs repr
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