Inhibition of Platelet Glycoprotein β₃ by Chimeric Monoclonal Antibody Prevents Arterial Thrombosis in Beagle Dogs,

Abstract 3357

In this present study in beagle dogs, we evaluated the antithrombotic efficacy of Pulaimab, the chimeric monoclonal antibodies SZ21-F(ab)₂ fragments against platelet glycoprotein (GP) β₃, in a modified Folts model. The Folts model is widely accepted to be effective and clinically relevant for testing potential anti-thrombotic agents, in this model the cyclic flow reductions (CFRs) are caused by platelet dependent thrombi that form under high-shear conditions at injured stenosed sites of an artery. Thirty beagle dogs of either sex, weighing 7.5 to 14 kg, were randomly divided into five groups of six (three females and three males), the details were following: negative control group (injected normal saline), positive control group (injected 0.2mg/Kg of Reopro), and three experimental groups [injected 0.2, 0.4, 0.8 mg/Kg of SZ21-F(ab)₂, respectively]. A dose range from 0.2 to 0.8 mg/kg of Pulaimab significantly reduced the CFRs by 21–73%, without reduction of platelet numbers and prolongation of the bleeding time. Ex vivo ADP-induced platelet aggregation was equally reduced. The present study demonstrates that the inhibition of platelet GP αIIbβ₃function by SZ21-F(ab)₂ is a powerful intervention to prevent platelet thrombus formation in injured arteries without thrombocytopenia and prolongation of the bleeding time. We therefore conclude that F(ab)₂ fragments of inhibitory anti-GPβ₃ antibodies may be useful compounds to prevent thrombosis.