In vivo efficacy of human recombinant factor IX produced by the human hepatoma cell line HuH‐7. (15th May 2015)

• Record Type: Journal Article
• Authors: Enjolras, N.; Perot, E.; Le Quellec, S.; Indalecio, A.; Girard, J.; Negrier, C.; Dargaud, Y.
• Is Part Of: Haemophilia. Volume 21:Number 4(2015:Jul.)
• Page Start: e317
• Page End: e321
• Publication Date: 2015-05-15
• Subjects: Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.12688
• Languages: English
• ISSNs: 1351-8216

Abstract

<abstract abstract-type="main" id="hae12688-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hae12688-sec-0001" sec-type="section"> <title>Introduction</title> <p>Post‐translational modifications of the CHO‐cell‐derived‐recombinant human factor IX (FIX) currently used for the treatment of hemophilia B (HB) are different from plasma derived FIX. Our previous studies described a rFIX (HIX) having better profile of post‐translational modifications than rFIX produced by CHO cells. The aim of the study consisted to verify the improved post‐translational modifications effect of HIX on <italic>in vivo</italic> recovery.</p> </sec> <sec id="hae12688-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>HIX has been produced in a bioreactor and then purified from supernatants. <italic>In vitro</italic> activation and activity were evaluated measured by thrombin generation tests (TGT) and compared to commercial molecules, Benefix<sup>®</sup>, Mononine<sup>®</sup>. The three molecules were then administrated (i.v.) to FIX‐knockout mice and two minutes after injection, blood samples were collected and subjected to human FIX‐specific‐ELISA and TGT.</p> </sec> <sec id="hae12688-sec-0003" sec-type="section"> <title>Results</title> <p>The clotting function of HIX, activation courses of HIX by FXIa and FVIIa‐TF complex appear normal as did activation of Benefix<sup>®</sup>, Mononine<sup>®</sup> and TG constants of each FIX were equivalent. After injection to HB mice, circulating HIX did not present any significant difference in term of antigen value with Benefix<sup>®</sup>. Intriguingly, TGT were clearly exhibiting a better velocity for HIX than Benefix<sup>®</sup> and Mononine<sup>®</sup>. These data suggested that HIX may improve <italic>in vivo</italic> coagulant efficacy in comparison with the two commercial FIX injected at the same dose.</p> </sec> <sec id="hae12688-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The study shows that HuH‐7‐derived‐rFIX has better <italic>in vivo</italic> haemostatic activity in hemophilia B mice compared to the reference rFIX molecule despite similar <italic>in vivo</italic> recovery rates, suggesting that HuH‐7 cells could represent an effective cellular system for production of rFIX.</p> </sec> </abstract>