IMMUNOASSAYS FOR TAXOL

TAXOL IS A PROMISING NEW ANTICANCER DRUG, ISOLATED FROM THE BARK OF THE WESTERN YEW (TAXUS BREVEFOLIA), AND IS CURRENTLYIN PHASE II CLINICAL TRIALS. DEVELOPMENT OF THIS DRUG IS IMPEDED BY A SUPPLY SHORTAGE. IDENTIFICATION OF NEW TAXOL SOURCES IS HAMPERED BY THE LACK OF SUITABLE ASSAYS FOR DETECTING TAXOL AND TAXANES IN BIOLOGICAL MATRICES. IN PHASE I OF THIS PROJECT, POLYCLONAL ANTISERA WERE RAISED AGAINST TAXOL HAPTENS AND A PROTOTYPE INDIRECT COMPETITIVE INHIBITION IMMUNOASSAY (CIEIA) WAS DEVELOPED. THIS CIEIA DETECTS TAXOL IN BARK EXTRACTS AND HUMAN PLASMA AT CONCENTRATIONS DOWN TO 0.5 NG/ML. SPECIFICITY TESTING DEMONSTRATED THAT THIS ASSAY WAS NEITHER TAXOL SPECIFIC NOR BROADLY CROSS-REACTIVE WITH RELATED TAXANES. THUS, WHILE THE FEASIBILITY OF AN IMMUNOASSAY FOR TAXOL HAS BEEN PROVEN, THE EXISTING POLYCLONAL-BASED ASSAY DOES NOT MEET THE NEEDS OF THE RESEARCH COMMUNITY. MONOCLONAL ANTIBODY (MAB)-BASED IMMUNOASSAYS ARE THE LOGICAL SOLUTION TO THE PROBLEM. IN PHASE II, MABS SPECIFIC FOR TAXOL, CEPHALOMANNINE, BACCATIN III, AND 10-DEACETYLBACCATIN III AND MABS WITH CROSS-REACTIVITY FOR THE TAXANES WILL BE PRODUCED. CIEIAS AND FIELD TESTS OF TWO TYPES, SPECIFIC FOR EACH OF THE FOUR SELECTED TAXANES AND "GENERIC TAXANE," WILL BE DEVELOPED WITH THESE MABS.