Schmidt Stefan R
AstraZeneca R&D, Södertälje, SE-15185 Södertälje, Sweden.
Curr Opin Drug Discov Devel. 2009 Mar;12(2):284-95.
As the genetic combination of originally separate proteins, fusion proteins are successful biopharmaceuticals. This review summarizes the fusion proteins that are approved for use in the clinic and those that are currently in clinical trials. Fusion proteins can be categorized into several groups according to their features. In the first group, effector molecules are fused to Fc domains, albumin or transferrin to extend the plasma half-life of the fusion product. In the second group, toxicity is conveyed by fusion proteins to toxins, enzymes or cytokines. The third application, which is not yet in clinical trials, utilizes fusion partners to enable novel delivery and targeting routes. Besides some specific disadvantages, many examples of fusion proteins suffer from the challenge of immunogenicity; however, future applications with novel fusion partners will reach beyond cancer, immunology and inflammation.
作为原本分离的蛋白质的基因组合，融合蛋白是成功的生物制药产品。本综述总结了已获批用于临床的融合蛋白以及目前正在进行临床试验的融合蛋白。融合蛋白可根据其特性分为几类。在第一类中，效应分子与Fc结构域、白蛋白或转铁蛋白融合，以延长融合产物的血浆半衰期。在第二类中，融合蛋白将毒性传递给毒素、酶或细胞因子。第三种应用（尚未进行临床试验）利用融合伴侣实现新的递送和靶向途径。除了一些特定的缺点外，许多融合蛋白的例子都面临免疫原性的挑战；然而，未来与新型融合伴侣的应用将超越癌症、免疫学和炎症领域。
