MONOCLONAL ANTIBODY ANTI-IDIOTYPE TUMOR VACCINES

THE OBJECTIVE OF THIS APPLICATION IS TO DEVELOP MONOCLONAL ANTIBODY (MOAB) ANTI-IDIOTYPE (ANTI-ID) TUMOR VACCINES FOR THE TREATMENT AND PREVENTION OF CANCER. THE SPECIFIC AIMS OF THE PHASE I PROPOSAL ARE TO DEFINE THE GENERAL PRINCIPLES FOR MAXIMIZING THE IN VIVO EFFICACY OF MOAB ANTI-ID TUMOR VACCINE PREPARATIONS. THIS WILL BE ACCOMPLISHED THROUGH A SYSTEMATIC COMPARISON OF ANTI-ID VACCINES REPRESENTING DIFFERENT TYPES OF TUMOR ASSOCIATED ANTIGENS (TAAS) IN A SOLID TUMOR ANIMAL MODEL. THESE PHASE I STUDIES WILL IDENTIFY THE CRITICAL VARIABLES AFFECTING THE THERAPEUTIC EFFICACY OF ANTI-ID TUMOR VACCINE PREPARATIONS. THE CONCLUSIONS DRAWN FROM THE PHASE I INVESTIGATIONS WILL OPTIMIZE THE DEVELOPMENT OF ANTI-ID TUMOR VACCINES FOR EVALUATION IN HUMAN CANCER PATIENTS IN PHASE II. IN CONTRAST TO CONVENTIONALLY PURIFIED TAA VACCINES, MOAB ANTI-ID PREPARATIONS CAN BE READILY PRODUCED IN LARGE QUANTITIES AND, UNLIKE RECOMBINANT DNA VACCINES, ANTI-ID VACCINES MAY BE EMPLOYED TO GENERATE IMMUNE RESPONSES AGAINST A WIDER VARIETY OF TAA DETERMINANTS, INCLUDING CARBOHYDRATE AND LIPID MOIETIES. THE RESULTS OF THE PHASE I AND II STUDIES, COMBINED WITH THE INHERENT ADVANTAGES OF ANTI-ID PREPARATIONS, MAY LEAD TO THE DEVELOPMENT OF NOVEL TUMOR VACCINE PRODUCTS USEFUL IN THE THERAPY OF HUMAN CANCERS.