| Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site. | |
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MedLine Citation:
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PMID: 20062929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (111)In-Oxine and post-surgical gamma camera imaging of (111)In-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. |
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Authors:
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Jin-an Jiao; Andrew B Kelly; Ulla M Marzec; Esperanza Nieves; Jorge Acevedo; Martin Burkhardt; Ana Edwards; Xiao-yun Zhu; Pierre-Andre Chavaillaz; Alice Wong; Jeffrey L Wong; Jack O Egan; Dean Taylor; Peter R Rhode; Hing C Wong |
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Publication Detail:
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Type: Journal Article Date: 2009-10-26 |
Journal Detail:
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Title: Thrombosis and haemostasis Volume: 103 ISSN: 0340-6245 ISO Abbreviation: Thromb. Haemost. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-11 Completed Date: 2010-03-30 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 7608063 Medline TA: Thromb Haemost Country: Germany |
Other Details:
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Languages: eng Pagination: 224-33 Citation Subset: IM |
Affiliation:
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Sunol Molecular Corporation, Miramar, Florida, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / administration & dosage, adverse effects, genetics, pharmacokinetics, pharmacology* Antibody Specificity Binding Sites Blood Coagulation / drug effects Blood Loss, Surgical / prevention & control CHO Cells Cricetinae Cricetulus Disease Models, Animal Dose-Response Relationship, Drug Endarterectomy Factor IX / metabolism Factor VIIa / metabolism Factor X / metabolism* Female Femoral Artery / surgery Fibrinolytic Agents / administration & dosage, adverse effects, pharmacokinetics, pharmacology* Hemorrhage / chemically induced Humans Injections, Intravenous Mice Mice, Inbred BALB C Pan troglodytes Recombinant Fusion Proteins / pharmacology Thromboplastin / antagonists & inhibitors*, immunology, metabolism Thrombosis / blood, etiology, prevention & control*, radionuclide imaging |
| Grant Support | |
ID/Acronym/Agency:
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R44 HL082397-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Fibrinolytic Agents; 0/Recombinant Fusion Proteins; 9001-28-9/Factor IX; 9001-29-0/Factor X; 9035-58-9/Thromboplastin; EC 3.4.21.21/Factor VIIa |
| Comments/Corrections | |
Comment In:
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Thromb Haemost. 2010 Jan;103(1):7-8
[PMID:
20062941
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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