DOMAIN-SPECIFIC ANTIBODIES TO HUMAN ERB-2/NEU PROTEIN

IN 20 TO 40 PERCENT OF HUMAN BREAST CANCERS, THE ERBB-2 OR NEU GENE IS AMPLIFIED, LEADING TO MRNA AND PROTEIN OVEREXPRESSION. THIS OVEREXPRESSION IS LIKELY TO BE INVOLVED IN EITHER THE INITIATION OR PROGRESSION OF THESE TUMOR CELLS. AMPLIFICATION OF THE ERBB-2 GENE HAS BEEN LINKED TO A POORER PROGNOSIS. IN PHASE I, MONOCLONAL AND POLYCLONAL ANTIBODIES TO EXTRACELLULAR AS WELL AS INTRACELLULAR REGIONS OF THE ERBB-2 PROTEIN WILL BE GENERATED. ANTIGEN WILL BE PREPARED FROM TWO SOURCES: MOUSE FIBROBLASTS EXPRESSING LARGE AMOUNTSOF THE HUMAN ERBB-2 PROTEIN AND BACTERIA GENETICALLY ENGINEERED TO EXPRESS SPECIFIC REGIONS OF THE ERBB-2 PROTEIN. THE RESULTING ANTIBODY PREPARATIONS WILL BE TESTEDFOR THEIR ABILITY TO SPECIFICALLY RECOGNIZE HUMAN ERBB-2 PROTEIN. IN PHASE II, THE USES OF THESE ANTIBODIES IN DIAGNOSIS AND THERAPY OF BREAST CANCER WILL BE EXPLORED.