BLOCKADE OF PLATELET GPIIB/IIIA RECEPTORS AS AN ANTITHROMBOTIC STRATEGY
BLOCKADE OF PLATELET GPIIB/IIIA RECEPTORS AS AN ANTITHROMBOTIC STRATEGY
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DOI：
10.1161/01.cir.92.9.2373
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发表时间：
1995-11-01
期刊：
影响因子：
37.8
通讯作者：
COLLER, BS
中科院分区：
文献类型：
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作者：
COLLER, BS
从实验室到临床，开发针对血小板GPIIb/IIIa受体的单克隆抗体7 E3，从基础科学实验室试剂到抗血栓药物是一个漫长的渐进过程。从一开始，我们就希望这种强大的新药物能让我们更好地定义GPIIb/IIIa受体的生物化学及其在血小板生理学和病理学中的作用，我首先回顾了自20世纪60年代以来我们对血小板生理学的理解的演变，以及为什么血小板GPIIb/IIIa受体似乎是抗血栓治疗的合理靶点。然后，我描述了我们的研究与7 E3阻断受体在实验动物模型的血栓形成。这些研究的结果鼓励我们尝试开发7 E3作为人类治疗剂。这一开发是数百人工作近十年的巨大努力，并最终于1994年12月获得美国食品和药物管理局批准c7 E3 Fab（阿昔单抗[ReoPro]）作为用于接受高风险冠状动脉血管成形术和斑块切除术的患者的联合治疗。对这一发展过程的详细描述超出了本文的范围，因此仅作简要描述。我从学术医学中心的研究工作台来回移动到药物开发世界的经历使我能够反思所涉及的过程，在本文的最后，我分享了我的一些想法和担忧。
Moving from bench to bedside in the development of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, from a basic science laboratory reagent to an antithrombotic drug was a long, incremental process. From the beginning, we hoped that this powerful new agent would allow us to define better the biochemistry of the GPIIb/IIIa receptor and its role in platelet physiology and pathology, and we dreamed that we might be able to use it to improve the therapy of patients with vascular disease.I first review the evolution of our understanding of platelet physiology since the 1960s and why the platelet GPIIb/IIIa receptor appeared to be a logical target for antithrombotic therapy. I then describe our studies with 7E3 to block the receptor in experimental animal models of thrombosis. The results of these studies encouraged us to try to develop 7E3 as a human therapeutic agent. The development was a monumental effort conducted by hundreds of people working for nearly a decade and culminated in the approval by the Food and Drug Administration of c7E3 Fab (abciximab [ReoPro]) in December 1994 as conjunctive therapy for use in patients undergoing high-risk coronary artery angioplasty and atherectomy. A detailed description of the developmental process is beyond the scope of this essay, so it is only briefly described. My experience in moving back and forth from the academic medical center research bench to the world of drug development has allowed me to reflect on the processes involved, and at the end of this essay, I share some of my thoughts and concerns.