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治疗中的Fc融合蛋白:最新观点。

Fc-fusion Proteins in Therapy: An Updated View.

作者信息

Jafari Reza, Zolbanin Naime M, Rafatpanah Houshang, Majidi Jafar, Kazemi Tohid

机构信息

Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz. Iran.

出版信息

Curr Med Chem. 2017;24(12):1228-1237. doi: 10.2174/0929867324666170113112759.

Abstract

Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for the treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among these medications Etanercept is the most effective in therapy. At present, eleven Fc-fusion proteins have been approved by FDA. There are novel Fc-fusion proteins which are in pre-clinical and clinical development. In this article, we review the molecular and biological characteristics of Fc-fusion proteins and then further discuss the features of novel therapeutic Fc-fusion proteins.

摘要

Fc融合蛋白由IgG抗体的Fc区域(铰链区-CH2-CH3)和一个期望的连接蛋白组成。Fc融合蛋白的Fc区域可与新生儿Fc受体(FcRn)结合,从而使其免于降解。首个治疗性Fc融合蛋白被用于治疗艾滋病。分子设计是Fc融合蛋白生产的第一阶段。Fc区域和连接蛋白中的氨基酸残基对融合蛋白的生物活性和亲和力非常重要。尽管治疗性单克隆抗体是最畅销的生物制品,但治疗性Fc融合蛋白在临床上的应用仍在进行中,其中依那西普在治疗中最为有效。目前,已有11种Fc融合蛋白获得美国食品药品监督管理局(FDA)批准。还有一些新型Fc融合蛋白正处于临床前和临床开发阶段。在本文中,我们综述了Fc融合蛋白的分子和生物学特性,然后进一步讨论新型治疗性Fc融合蛋白的特点。

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