DEVELOPMENT OF PALYTOXIN IMMUNOTOXINS PHASE I

THE OBJECTIVE OF THIS PROJECT IS TO ESTABLISH METHODS FOR CONJUGATING THE POTENT MARINE TOXIN, PALYTOXIN TO ANTIBODIES IN SUCH A WAY THAT SPECIFIC CYTOTOXICITY OF TARGET CELLS IS POSSIBLE. THE PRODUCT, IMMUNOPALYTOXIN (IPT), SHOULD BE EASILY PREPARED, HAVE HIGH SPECIFIC CYTOTOXIC ACTIVITY AND BE MINIMALLY TOXIC TO UNRELATED CELLSOR INTACT ANIMALS. THIS WORK WILL INVESTIGATE CHEMICAL LINKAGES BETWEEN PALYTOXIN AND ANTIBODIES AND CHARACTERIZE THE RESULTANT PRODUCT. ALL CYTOTOXICITY TESTING WILL BE CONDUCTED IN VITRO USING LYMPHOID CELL LINES. ANTIBODIES WILL BE USED WHICH RECOGNIZE SPECIFIC ANTIGENS ON THE TARGETCELLS. CYTOTOXICITY WILL BE MEASURED BY DYE EXCLUSION UPTAKE, PROTEIN SYNTHESIS AND CELL GROWTH CAPACITIES AFTER EXPOSURE TO IPT. SUCCESSFUL PRODUCTION OF IPT WHICH MEETS OUR DESIGN CRITERIA WILL HAVE APPLICATION IN BIOMEDICAL SITUATIONS WHERE SPECIFIC CYTOTOXICITY IS DESIRED. THERAPY OF CANCER, MODULATION OF IMMUNE RESPONSES, AND SPECIFIC CELLABLATION ARE IMPORTANT EXAMPLES OF HOW THIS PRODUCT COULD BEUSED. THE RESULTS OF THIS PHASE I PROJECT WILL LAY THE GROUNDWORK FOR IN VITRO TESTS IN ANIMALS AND, ULTIMATELY, HUMAN CLINICAL APPLICATIONS.