Flow cytometry in the preclinical development of biopharmaceuticals

Novel biomarkers are often required in the preclinical development of bioph armaceuticals in order to characterize pharmacologic and toxicologic effect s and to establish pharmacodynamic and pharmacokinetic relationships. Flow cytometry is uniquely suited for measurement of these biomarkers. Large num bers of single cells in a heterogeneous population can be rapidly identifie d and characterized with high accuracy and reproducibility. Cells are not d amaged by the detection system and can be subsequently sorted for further m orphologic or functional analysis. The availability of clinical instruments and a wide range of fluorescent probes have made this technology applicabl e for use in toxicologic clinical pathology. Row cytometry has played an in tegral role in the development of a monoclonal antibody to human CD4 (kelix imab, IDEC-CE9.1, SE 210396). Lymphocyte subset analysis and assays for exp ression, coating, and modulation of human CD4 were used for sequential asse ssment of the pharmacologic activity of keliximab in transgenic mice expres sing human CD4.