Elimination of factor VIII-specific B cells by immunotoxins composed of a single factor VIII domain fused to Pseudomonas exotoxin A

Journal of Thrombosis and Haemostasis : JTH
K BrettschneiderChristoph Königs

Abstract

Essentials There is still a need for novel therapeutic approaches for hemophilia A patients with inhibitors. A factor VIII domain was used as the targeting moiety for elimination of FVIII-specific B cells. The immunodominant C2 domain was fused to exotoxin A from Pseudomonas aeruginosa (hC2-ETA). Murine C2 domain-specific B cells were selectively and efficiently eliminated by hC2-ETA ex vivo. SUMMARY: Background Today, the most serious complication for patients with hemophilia A undergoing factor VIII (FVIII) replacement therapy is the development of neutralizing antibodies (inhibitors). Although inhibitors can be eradicated by application of high doses of FVIII, the immune tolerance induction therapy fails in up to 30% of patients. Hence, there is still an urgent need for novel therapeutic approaches for patients with persisting inhibitors. Objectives In the present study, the potential use of immunotoxins containing exotoxin A (ETA) from Pseudomonas aeruginosa for selective elimination of FVIII-specific B cells was explored. Methods The immunodominant C2 domain of human FVIII was used as a targeting moiety instead of the full-length FVIII protein and the resulting human C2 domain-ETA fusion protein (hC2-ETA) was produced in E...Continue Reading

References

Dec 1, 1993·British Journal of Anaesthesia·P A Flecknell
Oct 23, 1997·International Journal of Cancer. Journal International Du Cancer·U AltenschmidtW Wels
Mar 9, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Herm-Jan M BrinkmanJan A van Mourik
Apr 20, 2004·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Natalya M AnanyevaEvgueni L Saenko
Jul 17, 2004·Current Opinion in Hematology·Marc G Jacquemin, Jean-Marie R Saint-Remy
Oct 13, 2005·Haemophilia : the Official Journal of the World Federation of Hemophilia·M von Depka
Dec 22, 2006·Journal of Thrombosis and Haemostasis : JTH·J F HealeyP Lollar
Feb 19, 2008·Journal of Neuroimmunology·Thomas NachreinerMichael Stöcker
Oct 25, 2008·International Journal of Medical Microbiology : IJMM·Philipp Wolf, Ursula Elsässer-Beile
Jul 10, 2009·The Journal of Biological Chemistry·Shikha MalhotraK Mark Coggeshall
Jul 29, 2009·European Journal of Immunology·Stuart G Tangye, David M Tarlinton
Jun 12, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·B M ReipertH P Schwarz
Nov 16, 2010·International Journal of Cancer. Journal International Du Cancer·Mehmet Kemal TurStefan Barth
Nov 22, 2011·Blood·Charles R M HayUNKNOWN International Immune Tolerance Study
Mar 30, 2012·Lancet·Erik Berntorp, Amy D Shapiro
Sep 13, 2012·Critical Care : the Official Journal of the Critical Care Forum·Pashtoon M KasiHrishikesh S Kulkarni
Jun 13, 2014·Thrombosis and Haemostasis·C LeissingerS F Assmann
Oct 16, 2014·Journal of Thrombosis and Haemostasis : JTH·P M ZakasC B Doering
Feb 20, 2015·Science Translational Medicine·Nimesh GuptaSébastien Lacroix-Desmazes
Jan 8, 2016·British Journal of Cancer·Nikolaos Diamantis, Udai Banerji
Feb 13, 2016·Immunological Reviews·Ronit MazorIra Pastan
Mar 25, 2016·Thrombosis and Haemostasis·Anja SchmidtChristoph Königs
Oct 21, 2016·Haematologica·Bagirath GangadharanSébastien Lacroix-Desmazes

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