Makrides S C
Department of Cell Biology, PRAECIS Pharmaceuticals, Inc., Cambridge, MA 02139-1572, USA.
Pharmacol Rev. 1998 Mar;50(1):59-87.
The use of powerful methodologies in molecular biology, biochemistry, and physiology in the last 2 decades had led to impressive progress in our understanding of the mechanisms of complement activation and its role as either a protective or a pathogenic factor in human disease. With respect to disease pathogenesis, the complexity of the complement cascade provides opportunities for several different therapeutic targets within the complement pathways. More than a century after complement was first described, we are about to witness in the near future the availability of a variety of complement inhibitors for specific therapies. Progress in the area of xenotransplantation has been substantial, but formidable obstacles remain to selective inhibition of the factors that block successful clinical xenotransplantation. Bispecific antibodies, designed to enhance rather than inhibit existing complement pathways, hold strong promise for the clearance of viral and bacterial pathogens from the circulation.
在过去20年中,分子生物学、生物化学和生理学领域强大方法的应用,使我们对补体激活机制及其在人类疾病中作为保护或致病因素的作用有了令人瞩目的进展。关于疾病发病机制,补体级联反应的复杂性为补体途径中的几个不同治疗靶点提供了机会。在补体首次被描述一个多世纪后,我们即将在不久的将来看到多种用于特定治疗的补体抑制剂问世。异种移植领域已经取得了重大进展,但在选择性抑制阻碍临床异种移植成功的因素方面仍存在巨大障碍。旨在增强而非抑制现有补体途径的双特异性抗体,在清除循环中的病毒和细菌病原体方面具有很大的前景。