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Thromb Haemost 2010; 103(01): 224-233
DOI: 10.1160/TH09-06-0400
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site

Jin-an Jiao
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Andrew B. Kelly
2   Yerkes Regional Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA
,
Ulla M. Marzec
2   Yerkes Regional Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA
,
Esperanza Nieves
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Jorge Acevedo
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Martin Burkhardt
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Ana Edwards
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Xiao-yun Zhu
1   Sunol Molecular Corporation, Miramar, Florida, USA
3   Altor BioScience Corporation, Miramar, Florida, USA
,
Pierre-Andre Chavaillaz
1   Sunol Molecular Corporation, Miramar, Florida, USA
3   Altor BioScience Corporation, Miramar, Florida, USA
,
Alice Wong
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Jeffrey L. Wong
1   Sunol Molecular Corporation, Miramar, Florida, USA
,
Jack O. Egan
1   Sunol Molecular Corporation, Miramar, Florida, USA
3   Altor BioScience Corporation, Miramar, Florida, USA
,
Dean Taylor
1   Sunol Molecular Corporation, Miramar, Florida, USA
3   Altor BioScience Corporation, Miramar, Florida, USA
,
Peter R. Rhode
1   Sunol Molecular Corporation, Miramar, Florida, USA
3   Altor BioScience Corporation, Miramar, Florida, USA
,
Hing C. Wong
3   Altor BioScience Corporation, Miramar, Florida, USA
› Author Affiliations
Further Information

Publication History

Received: 24 June 2009

Accepted after major revision: 24 September 2009

Publication Date:
22 November 2017 (online)

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Summary

Tissue factor (TF) antagonists targeting the factor VII (FVII) binding domain have been shown to interrupt acute vascular thrombus formation without impairing haemostasis in non-human primates. In this study, we evaluate whether a human/mouse chimeric monoclonal antibody (ALT-836, formerly known as Sunol-cH36) blocking the factor X/factor IX (FX/FIX) binding site of tissue factor could achieve similar clinical benefits in an arterial thrombosis model induced by surgical endarterectomy in chimpanzees. In this model, sequential surgical endarterectomies on right and left superficial femoral arteries were performed 30 days apart in five chimpanzees. A bolus (1 mg/kg) of ALT-836 was injected intravenously immediately preceding the restoration of flow in the endarterectomised femoral artery. Pre-surgical labelling of autologous platelets using 111In-Oxine and post-surgical gamma camera imaging of 111In-platelet deposition at endarterectomy sites was performed. The manipulated arterial segments were harvested for patency analysis 30 days following surgery. The results indicate that ALT-836 was highly effective at reducing acute vascular thrombosis, with no significant variations in surgical blood loss and template-bleeding time in the treated group compared to the control animals. These data suggest that ALT-836 is an effective and safe antithrombotic agent in preventing TF-initiated vascular thrombogenesis without compromising haemostasis.

Keywords

Tissue factor / factor VII - animal models - arterial thrombosis - coagulation inhibitors
 

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