The goal of the proposed research is to produce human monoclonal antibodies reactive with human platelet adhesion receptors. These antibodies would be used as anti-platelet agents adjunctive to the clinical use of tissue plasminogen activator (TPA) in the treatment of acute myocardial infarction. Current TPA therapy has a 25-40% failure rate due to inadequate dissolution of clots or to rapid reocclusion of opened vessels. The most effective experimental agents that facilitate clot lysis by TPA, prevent reocclusion, and minimize hemorrhagic complications are murine monoclonal antibodies to the platelet adhesion receptor, GPIIb/IIIa. However, the intravenous administration of murine immunoglobulin incurs the risk of allergic reactions including anaphylaxis. To avoid these problems, human monoclonal antibodies to GPIIb/IIIa are needed; the recently developed reconstruction of a functional human immune system in SCID mice offers the opportunity to produce these antibodies.
