title: Role of receptor occupancy assays by flow cytometry in drug development.
abstract: The measurement of the binding of a biotherapeutic to its cellular target, receptor occupancy (RO), is increasingly important in development of biologically-based therapeutic agents. Receptor occupancy (RO) assays by flow cytometry describe the qualitative and/or quantitative assessment of the binding of a therapeutic agent to its cell surface target. Such RO assays can be as simple as measuring the number of cell surface receptors bound by an antireceptor therapeutic agent or can be designed to address more complicated scenarios such as internalization or shedding events once a receptor engages the administered therapeutic agent. Data generated from RO assays can also be used to model whether given doses of an experimental therapeutic agent and their administration schedules lead to predicted levels of receptor occupancy and whether the receptor is modulated (up or down) on cells engaged by the therapeutic agent. There are a variety of approaches that can be used when undertaking RO assays and with the ability to measure distinct subsets in heterogeneous populations, flow cytometry is ideally suited to RO measurements. This article highlights the importance of RO assays on the flow cytometric platform in the development of biotherapeutic agents.
authors.affiliation: Flow Contract Site Laboratory, LLC, Bothell, Washington, 98012.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Stewart
authors.affiliation: Amgen, Inc, Thousand Oaks, California, 91320.
authors.forename: Cherie L
authors.initials: CL
authors.lastname: Green
authors.affiliation: LabCorp Clinical Trials, Laboratory Corporation of America® Holdings, Brentwood, Tennessee, 37027.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jones
authors.affiliation: Medimmune, LLC, Mountain View, California, 94043.
authors.forename: Meina
authors.initials: M
authors.lastname: Liang
authors.affiliation: Alnylam Pharmaceuticals, Cambridge, Massachusetts, 02142.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Charles River Laboratories International, Inc, Reno, Nevada, 89511.
authors.forename: Danice E C
authors.initials: DE
authors.lastname: Wilkins
authors.affiliation: BioCytex, Marseille, 13010, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Moulard
authors.affiliation: Covance Central Laboratory Services, Geneva, 1217, Switzerland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czechowska
authors.affiliation: Eurofins Pharma Bioanalysis Services UK Limited, Park Abingdon, OX14 4RY, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lanham
authors.affiliation: ICON Laboratory Services, Farmingdale, New York, 11735.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McCloskey
authors.affiliation: Amgen, Inc, Thousand Oaks, California, 91320.
authors.forename: John
authors.initials: J
authors.lastname: Ferbas
authors.affiliation: PRA Healthsciences, Assen, TK, 9407, The Netherlands.
authors.forename: Barry W A
authors.initials: BW
authors.lastname: van der Strate
authors.affiliation: Xintela AB, Lund, SE-223 81, Sweden.
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Högerkorp
authors.affiliation: Takeda Pharmaceuticals, Cambridge, Massachusetts, 02139.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wyant
authors.affiliation: LabCorp Clinical Trials, Laboratory Corporation of America® Holdings, Brentwood, Tennessee, 37027.
authors.forename: Alan
authors.initials: A
authors.lastname: Lackey
authors.affiliation: Covance Central Laboratory Services, Indianapolis, Indiana, 46214.
authors.forename: Virginia
authors.initials: V
authors.lastname: Litwin
mesh_terms: D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use; D055808:Drug Discovery; D005434:Flow Cytometry / Q000379:methods* / Q000639:trends; D006801:Humans
chemical_list: D000906:Antibodies
keywords: biomarker; biotherapeutic; flow cytometry; receptor occupancy; target binding