PRODUCTION OF HUMAN ANTIPLATELET MONOCLONAL ANTIBODIES

THE GOAL OF THIS RESEARCH IS TO PRODUCE HUMAN MONOCLONAL ANTIBODIES REACTIVE WITH HUMAN PLATELET ADHESION RECEPTORS. THESE ANTIBODIES WOULD BE USED AS ANTIPLATELET AGENTS ADJUNCTIVE TO THE CLINICAL USE OF TISSUE PLASMINOGEN ACTIVATOR (TPA) IN THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION. CURRENT TPA THERAPY HAS A 25- TO 40-PERCENT 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 RECONSTRUCTIONOF A FUNCTIONAL HUMAN IMMUNE SYSTEM IN SCID MICE OFFERS THE OPPORTUNITY TO PRODUCE THESE ANTIBODIES.