Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents
To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-chain of human C3 is exchanged with homologous regions of the C-terminus of the β -chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.
KeywordsComplement Activation Complement Component Paroxysmal Nocturnal Hemoglobinuria Hybrid Protein Complement Deficiency
Part of the research was supported by Incode Biopharmaceutics Corporation, Lahaina, Hawaii, USA.
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