Tam S H, Sassoli P M, Jordan R E, Nakada M T
From Centocor, Malvern, PA 19355, USA.
Circulation. 1998 Sep 15;98(11):1085-91. doi: 10.1161/01.cir.98.11.1085.
Large, randomized, and blinded clinical trials (EPIC, EPILOG, and CAPTURE) have demonstrated that abciximab (ReoPro, chimeric 7E3 Fab) markedly reduces thrombotic events associated with percutaneous transluminal coronary interventions. The marked early benefits at 30 days were sustained at 6 months and 3 years. Initially developed because of its efficacy in blocking GP IIb/IIIa (alphaIIb/beta3) receptors on platelets, abciximab also binds with equivalent affinity to alpha(v)beta3.
This study presents a detailed characterization of the alphavss3 interaction, including the ability of abciximab to (1) bind with comparable affinity to alpha(v)beta3 and GP IIb/IIIa, (2) inhibit alpha(v)beta3 and GP IIb/IIIa-mediated cell adhesion in vitro with IC50 values approximating binding KD values, and (3) redistribute between GP IIb/IIIa and alpha(v)beta3 integrins in vitro.
As an antagonist of not only GP IIb/IIIa but also alpha(v)beta3, abciximab may provide additional clinical benefit in preventing alpha(v)beta3-mediated effects such as thrombin generation, clot retraction, or smooth muscle cell migration and proliferation. Abciximab binds with equivalent affinity to both GP IIb/IIIa and alphavss3 and redistributes between the 2 integrin receptors in vitro. Abciximab has been previously shown to circulate on platelets for up to 2 weeks. Taken together, these findings suggest that abciximab may have the ability to inhibit both GP IIb/IIIa and alpha(v)beta3 for extended periods.
大型随机双盲临床试验（EPIC、EPILOG和CAPTURE）已证明，阿昔单抗（ReoPro，嵌合7E3 Fab）可显著减少经皮腔内冠状动脉介入治疗相关的血栓形成事件。30天时的显著早期获益在6个月和3年时仍持续存在。阿昔单抗最初因其能有效阻断血小板上的糖蛋白IIb/IIIa（αIIb/β3）受体而研发，它还能以相同亲和力与α（v）β3结合。
本研究详细描述了αvβ3相互作用，包括阿昔单抗能够：（1）以相似亲和力与α（v）β3和糖蛋白IIb/IIIa结合；（2）在体外抑制α（v）β3和糖蛋白IIb/IIIa介导的细胞黏附，其半数抑制浓度（IC50）值接近结合解离常数（KD）值；（3）在体外于糖蛋白IIb/IIIa和α（v）β3整合素之间重新分布。
作为糖蛋白IIb/IIIa和α（v）β3的拮抗剂，阿昔单抗在预防α（v）β3介导的效应（如凝血酶生成、血块回缩或平滑肌细胞迁移与增殖）方面可能带来额外的临床益处。阿昔单抗与糖蛋白IIb/IIIa和αvβ3均以相同亲和力结合，并在体外于这两种整合素受体之间重新分布。此前已表明阿昔单抗可在血小板上循环长达2周。综上所述，这些发现提示阿昔单抗可能有能力长时间抑制糖蛋白IIb/IIIa和α（v）β3。
