Gene expression of cultured human chondrocytes as a model for assessing neutralization efficacy of soluble TNFα by TNFα antagonists. Issue 3 (May 2015)

• Record Type: Journal Article
• Authors: Barlič, Ariana; Žigon, Sara; Blejec, Andrej; Kregar Velikonja, Nevenka
• Is Part Of: Biologicals. Volume 43:Issue 3(2015:May)
• Page Start: 171
• Page End: 180
• Publication Date: 2015-05
• Subjects: Biological products -- Standards -- Periodicals; Biological Products -- Periodicals; Biological Products -- standards -- Periodicals; Produits biologiques -- Normes -- Périodiques; Biological products -- Standards; Periodicals; 615.37
• DOI: 10.1016/j.biologicals.2015.03.001
• Languages: English
• ISSNs: 1045-1056

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <p id="abspara0010">Tumor necrosis factor-alpha (TNFα) antagonists are efficacious in the treatment of various immune-mediated inflammatory diseases. Because of rapidly growing demand for developing new or biosimilar versions of these biologicals, the need to create <italic>in vitro</italic> testing models that best represent physiological conditions is increasing.</p> <p id="abspara0015">Primary human chondrocytes were used for potency evaluation and comparison between the molecular effects of anti-TNFα biologicals. Infliximab and etanercept were chosen to assess the suitability of chondrocyte cell culture for determination of anti-TNFα neutralization efficacy employing quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technology.</p> <p id="abspara0020">Use of both anti-TNFα biologics resulted in decrease of TNFα-stimulated expression of various matrix metalloproteinases, interleukins and other inflammation-related genes in our cell model. Significant differences in inhibition efficacy of etanercept and infliximab were observed, which were confirmed also on protein level. To evaluate the potency of anti-TNFα biologicals, a selection of TNFα-responsive target genes was made from the gene array data. The selected genes were employed in development of statistical model, which enables comparability of anti-TNFα biologicals.</p> <p id="abspara0025">The presented analytical approach is suitable for assessment of the neutralization efficacy of various anti-TNFα biologicals. As such, it can be used for additional comprehensive characterization and comparability of TNF antagonists in preclinical drug testing.</p> </sec> </abstract>