title: Complement depletion with humanised cobra venom factor: efficacy in preclinical models of vascular diseases.
abstract: 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.
authors.affiliation: Carl-Wilhelm Vogel, MD, PhD, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA, Tel.: +1 808 564 5979, Fax: +1 808 586 3077, E-mail: cvogel@cc.hawaii.edu.
authors.forename: Carl-Wilhelm
authors.initials: CW
authors.lastname: Vogel
authors.forename: David C
authors.initials: DC
authors.lastname: Fritzinger
authors.forename: W Brian
authors.initials: WB
authors.lastname: Gorsuch
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000494:pharmacology*; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000276:immunology
chemical_list: D003176:Complement C3; D051056:Complement Inactivating Agents; D004546:Elapid Venoms; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins; C016310:cobra venom factor; D003165:Complement System Proteins
keywords: CVF; Cobra venom factor; complement depletion; humanised cobra venom factor; reperfusion injury