Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Immune function tests for hazard identification: a paradigm shift in drug development.

Elizabeth R Gore1

  • 1Department of Safety Assessment, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. elizabeth.r.gore@gsk.com

Basic & Clinical Pharmacology & Toxicology
|April 21, 2006
PubMed
Summary

Regulatory requirements for immune function testing in drug development are debated. Optimization of T-cell dependent antibody response (TDAR) assays is ongoing to improve preclinical immunotoxicity risk assessments.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

<i>In vitro</i> and <i>in vivo</i> induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor.

Haematologica·2020
Same author

A hit deconstruction approach for the discovery of fetal hemoglobin inducers.

Bioorganic & medicinal chemistry letters·2018
Same author

Development of phenotypic screening assays for γ-globin induction using primary human bone marrow day 7 erythroid progenitor cells.

Journal of biomolecular screening·2013
Same author

Adequate immunotoxicity testing in drug development.

Toxicology letters·2004
Same author

Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation.

Toxicology·2004
Same author

Immunopharmacology of recombinant human interleukin-18 in non-human primates.

Cytokine·2002

Area of Science:

  • Pharmacology
  • Immunotoxicology
  • Regulatory Science

Background:

  • Regulatory agencies mandated routine immune function testing in preclinical drug development in 2000.
  • This mandate aimed to identify unintended immunosuppression but sparked debate due to differing international approaches.
  • Uncertainty regarding the predictive value of these tests prompted investigation by the International Council for Harmonisation (ICH).

Purpose of the Study:

  • To review the debate surrounding the necessity and utility of immune function tests in preclinical drug development.
  • To explore recommendations for optimizing T-cell dependent antibody response (TDAR) assays.
  • To enhance the sensitivity and predictability of immunotoxicity risk assessments.

Main Methods:

  • Evaluation of T-cell dependent antibody response (TDAR) using Sheep Red Blood Cell (SRBC) plaque assay.

Related Experiment Videos

  • Assessment of modified ELISA methods for TDAR using SRBC or keyhole limpet hemocyanin (KLH) as antigens.
  • Analysis of industry-wide survey data on the impact of pharmaceuticals on immune function.

    • Main Results:

    • A preliminary survey indicated that few pharmaceuticals impact immune function without affecting standard toxicology parameters.
    • Ongoing optimization of TDAR assays is crucial for establishing best practices.
    • The International Council for Harmonisation (ICH) is expected to issue guidelines that will influence future testing protocols.

    Conclusions:

    • The appropriateness of routine immune function testing remains a subject of discussion.
    • Optimizing TDAR methodology is essential for reliable preclinical immunotoxicity evaluations.
    • Further standardization and validation are needed to ensure the predictive value of immune function tests in drug development.