Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications.
Abciximab (ReoPro) is a mouse-human chimeric monoclonal antibody Fab fragment of the parent murine monoclonal antibody 7E3, and was the first of these agents approved for use as adjunct therapy for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Abciximab binds with high avidity to both the non-activated and activated form of the GPIIb/IIIa receptor of platelets, the major adhesion receptor involved in aggregation. Additional cardiovascular indications for abciximab are unstable angina, carotid stenting, ischemic stroke and peripheral vascular diseases. Abciximab also interacts with two other integrin receptors; the a av b b3 receptor, which is present in low numbers on platelets but in high density on activated endothelial and smooth muscle cells, and a aMb b2 integrin which is present on activated leukocytes. Cell types that express integrins GPIIb/IIIa and a av b b3 such as platelets, endothelial and tumor cells have been implicated in angiogenesis, tumor growth and metastasis. Since abciximab interacts with high avidity to integrins GPIIb/IIIa and a av b b3, it is reasonable to assume that it may possess anti-angiogenic properties in angiogenesis-related diseases, as well as anti-metastastatic properties in case of disseminating tumors expressing the target integrin receptors.
Cohen
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Cenrocor Inc. 200 Great Valley Parkway, Malvern, PA 19355, USA.,
Trikha
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Mascelli
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D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000503:physiopathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077284:Abciximab