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补体靶向治疗:C5和C5a靶向抑制的发展

Complement-targeted therapy: development of C5- and C5a-targeted inhibition.

作者信息

Horiuchi Takahiko, Tsukamoto Hiroshi

机构信息

Kyushu University Beppu Hospital, Beppu, Japan.

Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

出版信息

Inflamm Regen. 2016 Jun 3;36:11. doi: 10.1186/s41232-016-0013-6. eCollection 2016.

Abstract

The complement system is a major effector of humoral immunity and natural immunity. The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, and a lectin pathway. These pathways converge to a common pathway that activates C3. This pathway also leads to the formation of various bioactive molecules such as C5a and the formation of membrane attack complex on the surface of target cells. In the past, the only preparations with anti-complementary action were C1 inhibitors (C1-INH), but an anti-C5 monoclonal antibody (eculizumab) appeared a few years ago, and this antibody has yielded encouraging results. In addition, a C5a receptor (C5aR) antagonist is in the clinical trial phase, and this antagonist should also prove efficacious. Anti-complement agents have garnered attention as a new treatment strategy for refractory inflammatory diseases.

摘要

补体系统是体液免疫和天然免疫的主要效应器。补体系统有三条独立的补体激活途径:经典途径、替代途径和凝集素途径。这些途径汇聚到一条共同途径,激活C3。该途径还导致形成各种生物活性分子,如C5a,并在靶细胞表面形成膜攻击复合物。过去,唯一具有抗补体作用的制剂是C1抑制剂(C1-INH),但几年前出现了一种抗C5单克隆抗体(依库珠单抗),这种抗体已产生了令人鼓舞的结果。此外,一种C5a受体(C5aR)拮抗剂正处于临床试验阶段,这种拮抗剂也应证明是有效的。抗补体药物作为难治性炎症性疾病的一种新治疗策略已受到关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3f5/5725830/58d27994d665/41232_2016_13_Fig1_HTML.jpg

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