EVALUATION OF GALACTOSYLTRANSFERASE II AS A TUMOR MARKER

RECENT REPORTS BY SEVERAL INVESTIGATORS INDICATED SERUM LEVELS OF THE ISOENZYME OF B1-4-GALACTOSYLTRANSFERASE (GTII) CORRELATED WITH THE TUMOR BURDEN OF METASTIC CANCER PATIENTS. IN OVARIAN TUMOR PATIENTS, SUCCESSFUL CANCER THERAPY RESULTED IN DECREASED LEVELS OF SERUM GTII. PRELIMINARY STUDIES INDICATED THE VARIATION BETWEEN CANCER-ASSOCIATED AND NORMAL SERUM GT IS NOT IN THE GLYCOSYLATION BUT IN A SPECIFIC PEPTIDE FRAGMENT. THIS PROJECT WILL PURIFY CANCER-ASSOCIATED GT FROM A CELL LINE IDENTIFIED AS A GT PRODUCER. A DOUBLE LABELING TECHNIQUE AND PEPTIDE MAPPING WILL BE USED TO IDENTIFY THE PEPTIDE SEGMENTS THAT DIFFER STRUCTURALLY IN THE CANCER-ASSOCIATED AND NORMAL FORMS OF GT. STRUCTURAL IDENTIFICATION OF THE SPECIFIC PEPTIDE SEGMENT AND ANY STRUCTURAL MODIFICATION ASSOCIATED WITH IT, WILL BE USED TO PRODUCE HIGHLY SPECIFIC MONOCLONAL ANTIBODIES. ALL ASSAYS PERFORMED TO DATE ARE BASED ON ANTIBODIES PRODUCED FROM PARTIALLY PURIFIED GTII. THESE ANTIBODIES MAY CROSS REACT WITH OTHER SERUM FACTORS AND HAVE LOW SENSITIVITY. PHASE II EFFORTS WILL INCLUDE DEVELOPMENT OF A COMMERCIAL KIT TO MONITOR THE PROGRESS OF CANCER THERAPY AND PERFORMANCE OF DETAILED EVALUATION OF SENSITITIVY AND SPECIFICITY OF THE KIT, USING SERUM FROM CANCER PATIENTS.