THE LONG-TERM OBJECTIVE OF THE PROPOSAL IS TO CREATE AND EVALUATE THE EFFECTIVENESS OF MONOCLONAL ANTIBODY DIRECTED AGAINST THE RECEPTOR ON MALIGNANT CELLS RECOGNIZED BY ACTIVATED MACROPHAGES.

THE LONG-TERM OBJECTIVE OF THE PROPOSAL IS TO CREATE AND EVALUATE THE EFFECTIVENESS OF MONOCLONAL ANTIBODY DIRECTED AGAINST THE RECEPTOR ON MALIGNANT CELLS RECOGNIZED BY ACTIVATED MACROPHAGES. MACROPHAGES, WHEN ACTIVATED, RECOGNIZE AND DESTROY MALIGNANT CELLS. ACTIVATED MACROPHAGES DO NOT RECOGNIZE NONMALIGNANT CELLS. THE NATURE OF THIS RECEPTOR SITE IS UNKNOWN. IN THE CURRENT PHASE I PROPOSAL, USING NOVEL IMMUNIZATION PROTOCOLS, MONOCLONAL ANTIBODY WILL BE PRODUCED TO THAT RECOGNITION SITE. THE ANTIBODY WILL BE SCREENED IN APPROPRIATE ASSAYS FOR REACTIVITY WITH MALIGNANT AND NORMAL CELLS, INHIBITION OF BINDING, AND IMMUNOMODULATION. SUBSEQUENT PHASE II DEVELOPMENT WILL EVALUATE ITS ABILITY TO DESTROY TUMOR CELLS IN MODEL SYSTEMS BY VARIOUS MECHANISMS INCLUDING DIRECT TOXICITY, ANTIBODY-DEPENDENT CYTOTOXICITY AND THOROUGH IMMUNOTOXICITY CONJUGATES. ADDITIONAL DEVELOPMENT WOULD BE TO PROCEED TO PHASE I CLINICAL TRIALS. ALTERNATIVELY, THE ANTIBODY MAY BE USED TO PURIFY THE RECOGNITION SITE AND DEVELOP, USING THAT ANTIGEN, HUMAN MONOCLONAL ANTIBODIES.