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双特异性抗体:设计、治疗与前景

Bispecific antibodies: design, therapy, perspectives.

作者信息

Sedykh Sergey E, Prinz Victor V, Buneva Valentina N, Nevinsky Georgy A

机构信息

Laboratory of Repair Enzymes, Siberian Branch of Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, Novosibirsk State University, Novosibirsk, Russia.

出版信息

Drug Des Devel Ther. 2018 Jan 22;12:195-208. doi: 10.2147/DDDT.S151282. eCollection 2018.

Abstract

Antibodies (Abs) containing two different antigen-binding sites in one molecule are called bispecific. Bispecific Abs (BsAbs) were first described in the 1960s, the first monoclonal BsAbs were generated in the 1980s by hybridoma technology, and the first article describing the therapeutic use of BsAbs was published in 1992, but the number of papers devoted to BsAbs has increased significantly in the last 10 years. Particular interest in BsAbs is due to their therapeutic use. In the last decade, two BsAbs - catumaxomab in 2009 and blinatumomab in 2014, were approved for therapeutic use. Papers published in recent years have been devoted to various methods of BsAb generation by genetic engineering and chemical conjugation, and describe preclinical and clinical trials of these drugs in a variety of diseases. This review considers diverse BsAb-production methods, describes features of therapeutic BsAbs approved for medical use, and summarizes the prospects of practical application of promising new BsAbs.

摘要

在一个分子中含有两个不同抗原结合位点的抗体(Abs)被称为双特异性抗体。双特异性抗体(BsAbs)最早在20世纪60年代被描述,首批单克隆双特异性抗体于20世纪80年代通过杂交瘤技术产生,第一篇描述双特异性抗体治疗用途的文章于1992年发表,但在过去10年中,致力于双特异性抗体的论文数量显著增加。对双特异性抗体的特别关注源于其治疗用途。在过去十年中,两种双特异性抗体——2009年的卡妥索单抗和2014年的贝林妥欧单抗被批准用于治疗。近年来发表的论文致力于通过基因工程和化学偶联产生双特异性抗体的各种方法,并描述了这些药物在多种疾病中的临床前和临床试验。本综述考虑了多种双特异性抗体制备方法,描述了已批准用于医学用途的治疗性双特异性抗体的特点,并总结了有前景的新型双特异性抗体的实际应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/b63f997e5874/dddt-12-195Fig1.jpg

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