MABS TO TUMOR SUPPRESSOR GENE DCC-ENCODED PROTEIN

EVIDENCES SUGGEST THAT INACTIVATION OF SPECIFIC "TUMOR SUPPRESSOR" GENES CONTRIBUTES TO THE FORMATION OF SEVERAL HUMAN CANCER TYPES INCLUDING RETINOBLASTOMA (RB), OSTEOSARCOMA, WILMS' TUMOR, NEUROFIBROMATOSIS, SMALL CELL LUNG CARCINOMA, AND ADENOCARCINOMAS OF BREAST AND COLON. THE TUMOR SUPPRESSOR GENES RB,P53,WT1,NF-1,DCC AND MCC HAVE BEEN CLONES. THE P 53, DCC AND MCC GENES WERE THOUGHT TO BE ASSOCIATED WITH THE PROGRESSIONS OF COLON CARCINOMAS. WE HAVE RECENTLY DEVELOPED ANTI-RB MAB-BASED IMMUNOASSAYS TO STUDY RB PROTEIN EXPRESSION IN HUMAN OSTEOSARCOMAS AND OTHER SOFT-TISSUE SARCOMAS. OUR RESULTS REVEAL THAT THE ABSENCE OF RB PROTEIN IN THESE TUMORS MAY HAVE A SIGNIFICANT PROGNOSTIC VALUE. WE HAVE ALSO PRODUCED MONOCLONAL ANTIBODIES AGAINST DISTINCT EPITOPES OF THE HUMAN P53 PROTEIN. THE PRIMARY GOAL IS TO PRODUCE A PANEL OF MABS AGAINST DISTINCT EPITOPES OF THE HUMAN DCC PROTEIN. THESE MABS WILL BE USED IN DEVELOPMENT OF SENSITIVE AND SPECIFIC IMMUNOASSAYS FOR DCC-RELATED CANCERS. THESE MABS WILL ALSO BE USEFUL FOR CHARACTERIZING THE DCC PROTEIN AND ASSESSING THE FUNCTION OF THE DCC PROTEIN IN HUMAN NEOPLASIA. THE SPECIFIC AIMS ARE: 1) TO GENERATE A PANEL OF MABS RECOGNIZING DISTINCT EPITOPES OF HUMAN DCC PROTEINS, 2) TO CHARACTERIZE THE EPITOPES RECOGNIZED BY HUMAN DCC-SPECIFIC MABS, AND 3) TO DEVELOP SENSITIVE AND SPECIFIC IMMUNOASSAYS FOR DCC-RELATED CANCER DIAGNOSIS. THE KNOWLEDGE DERIVED AND THE TESTS DEVELOPED FROM THESE MABS WILL BE VERY IMPORTANT FOR PHASE II CLINICAL APPLICATIONS SUCH AS PROSPECTIVE OR PROGNOSTIC STUDIES.