Binding of Abciximab to αVβ3 and Activated αMβ2 Receptors: With a Review of Platelet-Leukocyte Interactions

Introduction

Murine monoclonal antibody 7E3, as well as the derivatives of 7E3 used in vivo [7E3-F(ab’)₂, 7E3 Fab’, mouse/human chimeric 7E3 Fab (c7E3 Fab; abciximab; ReoPro^™)], inhibit platelet aggregation induced by physiologic and pathologic agonists by binding to the platelet glycoprotein (GP) IIb/IIIa receptor.^1,2 This biological activity formed the basis of its development as an antithrombotic agent to prevent and treat plateletmediated ischemic cardiovascular disease. During its development, 7E3 was reported to also react with two other integrin receptors, the αVβ3 “vitronectin” receptor (CD51/CD61)^3,4 and at least one activation-dependent conformation of the αMβ2 or “Mac-1” receptor (CD11b/CD18).⁵ Whereas both αVβ3 and αMβ2 have been implicated in a number of different physiologic and pathologic processes, it is possible that some effects of abciximab are due to its reactivity with one or the other of these receptors. Moreover, the reactivity of abciximab with these receptors opens up the possibility that abciximab, or other agents that inhibit these receptors, may be useful in preventing or treating disorders in which these receptors play a role. This review will address these issues.

Note: Dr. Coller is an inventor of abciximab, and in accordance with Federal law and the policies of the Research Foundation of the State University of New York, he shares in royalties paid to the Foundation for sales of abciximab.

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