WE PROPOSE TO DEVELOP A STANDARDIZED KIT OF MONOCLONAL ANTIBODY (MOAB) CONJUGATED WITH A NOVEL BIOLOGICAL CATALYST TOXIN TO BE USED FOR THE EX VIVO ELIMINATION OF NEOPLASTIC CELLS FROM HUMAN AUTOLOGOUS BONE MARROW GRAFTS.

WE PROPOSE TO DEVELOP A STANDARDIZED KIT OF MONOCLONAL ANTIBODY (MOAB) CONJUGATED WITH A NOVEL BIOLOGICAL CATALYST TOXIN TO BE USED FOR THE EX VIVO ELIMINATION OF NEOPLASTIC CELLS FROM HUMAN AUTOLOGOUS BONE MARROW GRAFTS. THE TECHNICAL OBJECTIVES ARE TO PREPARE A TOXIN-CONJUGATED MURINE MOAB THAT WILL SPECIFICALLY BIND TO ANTIGEN POSITIVE NEOPLASTIC CELLS PRESENT IN AUTOLOGOUS BONE MARROW GRAFTS BUT NOT TO ANTIGEN NEGATIVE CELLS. THIS TOXIN-CONJUGATED MOAB WILL EFFICIENTLY LYSE THE ANTIGEN POSITIVE CELLS TO WHICH IT IS BOUND WITHOUT SUBSTANTIALLY AFFECTING ANTIGEN NEGATIVE STEM CELLS NECESSARY FOR RESTORATION OF HEMATOPOIETIC AND IMMUNOLOGIC THE METHODS OUTLINED IN THIS PROPOSAL ARE BASED ON A CLASS OF CATALYST-TOXINS THAT HAVE NOT PREVIOUSLY BEEN CONSIDERED FOR APPLICATION TO EX VIVO CYTOLYSIS OF NEOPLASTIC CELLS. THESE TOXINS HAVE BEEN EXTENSIVELY STUDIED AND SHOWN TO MEDIATE HIGHLY EFFICIENT LYSIS OF NEOPLASTIC CELLS. MOREOVER, IT HAS BEEN ESTABLISHED THAT THESE CATALYSTS CAN BE CONJUGATED TO MOAB WITH RETENTION OF ANTIBODY SPECIFICITY AND TOXIN ACTIVITY. BY CONJUGATING THESE AGENTS TO MONOCLONAL ANTIBODIES DIRECTED TOWARD NEOPLASTIC CELL ANTIGENS, WE HOPE TO PRODUCE AN EFFECTIVE AND COMMERCIALLY ATTRACTIVE REAGENT SYSTEM FOR PURGING TUMOR CELLS FROM BONE MARROW INTENDED