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

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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 (αIIb/β3) receptors on platelets, abciximab also binds with equivalent affinity to αvβ3. Methods and Results—This study presents a detailed characterization of the αvβ3 interaction, including the ability of abciximab to (1) bind with comparable affinity to αvβ3 and GP IIb/IIIa, (2) inhibit αvβ3 and GP IIb/IIIa–mediated cell adhesion in vitro with IC50 values approximating binding KD values, and (3) redistribute between GP IIb/IIIa and αvβ3 integrins in vitro. Conclusions—As an antagonist of not only GP IIb/IIIa but also αvβ3, abciximab may provide additional clinical benefit in preventing αvβ3-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 αvβ3 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 αvβ3 for extended periods.

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