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单克隆抗体的发展历程——进展、尚存挑战及未来创新

The history of monoclonal antibody development - Progress, remaining challenges and future innovations.

作者信息

Liu Justin K H

机构信息

Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London, E1 2AD, UK.

出版信息

Ann Med Surg (Lond). 2014 Sep 11;3(4):113-6. doi: 10.1016/j.amsu.2014.09.001. eCollection 2014 Dec.

Abstract

As medicine progresses into a new era of personalised therapy, the use of monoclonal antibodies to treat a wide range of diseases lies at the heart of this new forefront. Since the licencing of the first monoclonal antibody for clinical use 30 years ago, the monoclonal antibody industry has expanded exponentially and is now valued at billions of dollars. With major advances in genetic sequencing and biomedical research, much research into monoclonal antibodies now focuses on identifying new targets for development and maximising their efficacy for use in clinical practice. However, a balance has to be struck with regards to reducing numbers of side-effects and overall economic cost, which arguably somewhat blighted their early clinical and commercial successes. Nowadays, there are approximately 30 monoclonal antibodies that have been approved for use in clinical practice with many more currently being tested in clinical trials. Some of the current major limitations include: the use of inefficient models for generation, a lack of efficacy and issues of cost-effectiveness. Some of the current research focuses on ways to improve the efficacy of existing monoclonal antibodies through optimising their effects and the addition of beneficial modifications. This review will focus on the history of monoclonal antibody development - how it has increasingly moved away from using laborious animal models to a more effective phage display system, some of the major drawbacks from a clinical and economical point of view and future innovations that are currently being researched to maximise their effectiveness for future clinical use.

摘要

随着医学进入个性化治疗的新时代,单克隆抗体在治疗多种疾病中的应用处于这一前沿领域的核心位置。自30年前首个单克隆抗体获批用于临床以来,单克隆抗体产业呈指数级增长,目前价值数十亿美元。随着基因测序和生物医学研究的重大进展,目前对单克隆抗体的许多研究集中在确定新的开发靶点,并在临床实践中最大限度地提高其疗效。然而,在减少副作用数量和总体经济成本方面必须取得平衡,这在一定程度上影响了它们早期的临床和商业成功。如今,约有30种单克隆抗体已获批用于临床实践,还有更多正在临床试验中进行测试。当前一些主要限制包括:用于生产的模型效率低下、缺乏疗效以及成本效益问题。目前一些研究集中在通过优化现有单克隆抗体的作用和添加有益修饰来提高其疗效的方法上。本综述将聚焦单克隆抗体的发展历程——它如何越来越多地从使用费力的动物模型转向更有效的噬菌体展示系统,从临床和经济角度来看的一些主要缺点,以及目前正在研究的未来创新,以最大限度地提高其在未来临床应用中的有效性。

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