Abciximab (ReoPro, Chimeric 7E3 Fab) Demonstrates Equivalent Affinity and Functional Blockade of Glycoprotein IIb/IIIa and α v β 3 Integrins

Abstract

Background —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 (α IIb /β 3 ) receptors on platelets, abciximab also binds with equivalent affinity to α v β 3 . Methods and Results —This study presents a detailed characterization of the α v β 3 interaction, including the ability of abciximab to (1) bind with comparable affinity to α v β 3 and GP IIb/IIIa, (2) inhibit α v β 3 and GP IIb/IIIa–mediated cell adhesion in vitro with IC 50 values approximating binding K D values, and (3) redistribute between GP IIb/IIIa and α v β 3 integrins in vitro. Conclusions —As an antagonist of not only GP IIb/IIIa but also α v β 3 , abciximab may provide additional clinical benefit in preventing α v β 3 -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 α v β 3 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 α v β 3 for extended periods.