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Thromb Haemost 2015; 113(03): 548-552
DOI: 10.1160/TH14-04-0300
Theme Issue Article
Schattauer GmbH

Complement depletion with humanised cobra venom factor: Efficacy in preclinical models of vascular diseases

Carl-Wilhelm Vogel
1   University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
2   Department of Pathology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
,
David C. Fritzinger
1   University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
,
Brian W. Gorsuch
3   Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Boston, Massachusetts, USA
,
Gregory L. Stahl
3   Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Boston, Massachusetts, USA
› Author Affiliations
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Publication History

Received: 02 April 2014

Accepted after minor revision: 07 May 2014

Publication Date:
29 November 2017 (online)

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Summary

The complement system is an intrinsic part of the immune system and has important functions in both innate and adaptive immunity. On the other hand, inadvertent or misdirected complement activation is also involved in the pathogenesis of many diseases, contributing solely or significantly to tissue injury and disease development. Multiple approaches to develop pharmacological agents to inhibit complement are currently being pursued. We have developed a conceptually different approach of not inhibiting but depleting complement, based on the complement-depleting activities of cobra venom factor (CVF), a non-toxic cobra venom component with structural and functional homology to complement component C3. We developed a humanised version of CVF by creating human complement component C3 derivatives with complement-depleting activities of CVF (humanised CVF) as a promising therapeutic agent for diseases with complement pathogenesis. Here we review the beneficial therapeutic effect of humanised CVF in several murine models of vascular diseases such as reperfusion injury.

Keywords

Cobra venom factor - humanised cobra venom factor - CVF - complement depletion - reperfusion injury
 

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