Journal article
Delayed targeting of CD39 to activated platelet GPIIb/IIIa via a single-chain antibody: Breaking the link between antithrombotic potency and bleeding?
JD Hohmann, X Wang, S Krajewski, C Selan, CA Haller, A Straub, EL Chaikof, HH Nandurkar, CE Hagemeyer, K Peter
Blood | AMER SOC HEMATOLOGY | Published : 2013
Abstract
The ecto-nucleoside triphosphate diphosphohydrolase CD39 represents a promising antithrombotic therapeutic. It degrades adenosine 59-diphosphate (ADP), a main platelet activating/recruiting agent. We hypothesized that delayed enrichment of CD39 on developing thrombi will allow for a low and safe systemic concentration and thus avoid bleeding. We use a single-chain antibody (scFv, specific for activated GPIIb/IIIa) for targeting CD39. This should allow delayed enrichment on growing thrombi but not on the initial sealing layer of platelets, which do not yet express activated GPIIb/IIIa. CD39 was recombinantly fused to an activated GPIIb/IIIa-specific scFv (targ-CD39) and a nonfunctional scFv (..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
J.D.H. was supported by a scholarship from the University of Melbourne, X. W. was supported by a scholarship from Monash University, and S. K. and A. S. were supported by grants from the German Research Foundation (STR 687/1-1). C. H. and E. L. C. were supported by the National Institutes of Health, C. E. H. was supported by a fellowship from the National Health and Medical Research Council of Australia, and K. P. was supported by a Future Fellowship from the Australian Research Council.