IMMUNOASSAYS FOR TAXOL

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DESCRIPTION: (Adapted from the applicant's abstract) Taxol is a promising new anti-cancer drug, isolated from the bark of the Western Yew (Taxus brevefolia) currently in Phase II clinical trials. Further 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 study, MAbs specific for taxol, cephalomannine, baccatin III and l0-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. The current need to assay large numbers of Taxus tissue samples indicates a substantial market for taxane immunoassays could exist.