IMMUNOAFFINITY ADSORPTION METHODS FOR TAXOL

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The technical feasibility of separating milligram amounts of the anti- cancer drug taxol from closely related analogs by immunoaffinity chromatography (IAC) was demonstrated in Phase I research. At the analytical scale, this technique may be useful for taxol sample preparation prior to HPLC or HPLC-MS analysis. Other IAC systems, using different anti-taxane mAbs, can now be investigated for isolation of other taxol congeners and metabolites. HBG already has available mAbs which are baccatin III-specific and taxane-class specific. IAC methods incorporating these mAbs may be applied to the study of basic and clinical research questions, such as clinical pharmacokinetics, identification of alternative supply sources, and isolation of new congeners and metabolites. The techniques of molecular biology make possible the extension of taxol IAC methodology to the preparative scale. Cloned low molecular weight antibody fragments can be expressed in microbial culture for use in large- scale isolation procedures. These fragments, which are less bulky than whole immunoglobulin, should permit improved column capacity and flow rate, while retaining the desired selectivity. The cloning procedures also provide the genetic information necessary for ancillary studies, such as the construction of fusion proteins, low molecular weight peptide mimetics, and sequence/activity studies.