Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents

被引：13

作者：

Fritzinger, David C. ^{[1
]}

Hew, Brian E. ^{[1
]}

Lee, June Q. ^{[1
]}

Newhouse, James ^{[2
]}

Alam, Maqsudul ^{[3
]}

Ciallella, John R. ^{[4
]}

Bowers, Mallory ^{[4
]}

Gorsuch, William B. ^{[5
]}

Guikema, Benjamin J. ^{[5
]}

Stahl, Gregory L. ^{[5
]}

Vogel, Carl-Wilhelm ^{[1
]}

机构：

[1] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA

[2] Maui High Performance Comp Ctr, Kihei, HI 96753 USA

[3] Univ Hawaii, Honolulu, HI 96822 USA

[4] Melior Discovery Corp, Exton, PA 19341 USA

[5] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA

来源：

CURRENT TOPICS IN COMPLEMENT II | 2008年 / 632卷

关键词：

D O I：

10.1007/978-0-387-78952-1_21

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 alpha-chain of human C3 is exchanged with homologous regions of the C-terminus of the beta-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.

引用

页码：293 / 307

页数：15

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