Paclitaxel has been approved for the treatment of refractory ovarian and breast cancers. It is currently in clinical trials for the treatment of lung and colon cancer. Paclitaxel production from cultured plant cells is both ecologically friendly and flexible and remains a viable alternative to conventional processes where the paclitaxel is directly extracted from plant raw material. In phase I studies, a novel screening method, the 'Enhanced Xechem Integrated Screening Technique' (EXISTtm) that integrates process operations, into screening will be used to select Taxus spp. suspension cell lines for high level paclitaxel production. EXISTtm is both simple and rapid and reduces the optimization steps required for a cell suspension based process. The specific aims are: . select an insoluble, liquid second phase for in-situ removal of paclitaxel . screen for high yielding, high secreting, Taxus spp. cell lines using EXISTtm . optimize culture conditions for the highest accumulation of paclitaxel in the second phase . apply secondary production enhancement strategies such as elicitation, precursor feeding and second phase recycling to the two-phase cultures The optimum conditions of the cell lines selected by EXISTtm will be determined and additional enhancement strategies further integrated to reach economically viable production levels.Proposed commercial application:Attaining the goals specified in this proposal would make the economic viability for paclitaxel tenable. This would also provide the impetus for manufacture of other scarce phytopharmaceuticals.National Cancer Institute (NCI)
