ANTIBODIES USEFUL FOR PREDICTING RESPONSE TO CHEMOTHERAPY

CHEMOTHERAPY HAS PROVEN USEFUL IN THE MANAGEMENT OF MANY DIFFERENT TYPES OF CANCERS. HOWEVER, TWO MAJOR IMPEDIMENTS TO EFFECTIVE CHEMOTHERAPY ARE THE INABILITY TO PREDICT WHICHPATIENTS WOULD RESPOND TO A GIVEN DRUG REGIMEN AND THE DEVELOPMENT OF MULTIPLE DRUG RESISTANCE IN A LARGE NUMBER OFCANCER PATIENTS WHO INITIALLY RESPOND WELL TO CHEMOTHERAPY. DIAGNOSTIC REAGENTS THAT WOULD BE ABLE TO DETERMINE IF AND WHEN A PATIENT DEVELOPED DRUG RESISTANCE ASWELL AS REAGENTS CAPABLE OF PREDICING THE RESPONSIVENESS OF AN INDIVIDUAL PATIENT TO A GIVEN CHEMOTHERAPEUTIC REGIMEN PRIOR TO TREATMENT WOULD GREATLY EXPAND THE UTILITY OF AVAILABLE ANTICANCER DRUGS. THE PRIMARY GOAL OF THIS PROJECT IS TO DEVELOP SENSITIVE IMMUNOLOGICAL REAGENTS CAPABLE OF QUANTITATING AND IDENTIFYING THE AMOUNT OF TOPOISOMERASE II PRESENT IN A CANCEROUS CELL. BECAUSE THE AMOUNT OF TOPOISOMERASE II PRESENT IN A CELL IS WELL CORRELATED WITH THE THERAPEUTIC UTILITY OF MANY ANTICANCER DRUGS, THESE MONOCLONAL ANTIBODIES WILL BE USEFUL IN PRESCRIBING AND MONITORING THE EFFECTIVENESS OF A CHEMOTHERAPEUTIC REGIMEN. ADDITIONALLY, SINCE IN SOME CASES ALTERATIONS IN TOPOISOMERASE II ARE RESPONSIBLE FOR DRUG RESISTANCE, ANTIBODIES THAT CAN IDENTIFY CANCER CELLS THAT CONTAIN DRUG-RESISTANT TOPOISOMERASE II WILL ALSO BE DEVELOPED. THESE ANTIBODIES WOULD BE FORMATTED TO DEVELOP IMMUNOLOGICALTESTS CAPABLE OF QUANTITATING LEVELS OF TOPOISOMERASE II AS A MEDICAL AND BASIC RESEARCH TOOL.