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Flow Cytometry in the Preclinical Development of Biopharmaceuticals
Kent A. Gossett
SmithKline Beecham Pharmaceuticals, 709 Swedeland Road (UE 0360), King of Prussia, Pennsylvania 19406, kent_gossett{at}sbphrd.com.
Padma K. Narayanan
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Donna M. Williams
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Elizabeth R. Gore
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Danuta J. Herzyk
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Timothy K. Hart
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Teresa S. Sellers
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Novel biomarkers are often required in the preclinical development of biopharmaceuticals in order to characterize pharmacologic and toxicologic effects and to establish pharmacodynamic and pharmacokinetic relationships. Flow cytometry is uniquely suited for measurement of these biomarkers. Large numbers of single cells in a heterogeneous population can be rapidly identified and characterized with high accuracy and reproducibility. Cells are not damaged by the detection system and can be subsequently sorted for further morphologic or functional analysis. The availability of clinical instruments and a wide range of fluorescent probes have made this technology applicable for use in toxicologic clinical pathology. Flow cytometry has played an integral role in the development of a monoclonal antibody to human CD4 (keliximab, IDEC-CE9.1, SB 210396). Lymphocyte subset analysis and assays for expression, coating, and modulation of human CD4 were used for sequential assessment of the pharmacologic activity of keliximab in transgenic mice expressing human CD4.
Key Words: Flow cytometry • biopharmaceuticals • pharmacology • toxicology • drug development • animal
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Toxicologic Pathology, Vol. 27, No. 1,
32-37 (1999)
DOI: 10.1177/019262339902700107
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P J Bugelskil, D J Herzykl, S Rehm, A G Harmsen, E V Gore, D M Williams, B E Maleeff, A M Badger, A Truneh, S R O'Brien, et al.
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