title: The T-cell-dependent antibody response assay in nonclinical studies of pharmaceuticals and chemicals: study design, data analysis, interpretation.
abstract: The T-cell-dependent antibody response (TDAR) assay is a measure of immune function that is dependent upon the effectiveness of multiple immune processes, including antigen uptake and presentation, T cell help, B cell activation, and antibody production. It is used for risk and safety assessments, in conjunction with other toxicologic assessments, by the chemical and pharmaceutical industries, and research and regulatory agencies. It is also employed to evaluate investigational drug efficacy in animal pharmacology studies, provide evidence of biological impact in clinical trials, and evaluate immune function in patients with primary or secondary immunodeficiency diseases. Various immunization schemes, analytical methods, approaches to data analysis, and data interpretations are in use. This manuscript summarizes some recommended practices for the conduct and interpretation of the assay in animal studies.
authors.affiliation: Amgen, Seattle, WA, USA. Electronic address: hlebrec@amgen.com.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lebrec
authors.affiliation: Sanofi-Aventis R&D, Montpellier, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Molinier
authors.affiliation: The Dow Chemical Company, Midland, MI, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Boverhof
authors.affiliation: Pfizer, Inc., Groton, CT, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Collinge
authors.affiliation: Bristol-Myers Squibb Company, New Brunswick, NJ, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Freebern
authors.affiliation: Novartis Institutes for Biomedical Research Inc., East Hanover, NJ, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Henson
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Mytych
authors.affiliation: Department of Pediatrics, University of Washington, and Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.affiliation: Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wange
authors.affiliation: Office of Pesticides Programs, US Environmental Protection Agency, Washington, DC, USA.
authors.forename: Yung
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Covance Inc., Madison, WI, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Arrington
authors.affiliation: Charles River Laboratories, Montreal, Canada.
authors.forename: Marie Soleil
authors.initials: MS
authors.lastname: Christin-Piché
authors.affiliation: MedImmune Ltd., Cambridge, UK.
authors.forename: Jacintha
authors.initials: J
authors.lastname: Shenton
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001681:Biological Assay / Q000379:methods*; D002986:Clinical Trials as Topic; D004345:Drug Industry / Q000379:methods; D006801:Humans; D012107:Research Design; D018570:Risk Assessment / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*
keywords: Immunotoxicity; Nonclinical studies; TDAR