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Flow Cytometry in the Preclinical Development of Biopharmaceuticals

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

Toxicologic Pathology, Vol. 27, No. 1, 32-37 (1999)
DOI: 10.1177/019262339902700107


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