Although taxol, paclitaxel, is one of the most promising anticancer drugs, the supply of taxol has not met the market demands. To date taxol production is limited and dependent on extraction from bark of yew tree, Taxus brevifolia. Chemical synthesis of taxol gives low yield, semi- synthetic production requires a very large supply of plant material. Plant cell cultures in batch reactors provide low productivity. The overall goal of our project is to develop an economically viable continuous plant cell culture process that will provide sufficient taxol for wide- spread human therapy. This system overcomes the limitations of typical plant cell cultures by separating the immobilized cell mass into layers and controlling channeling while maintaining high cell density and a uniform oxygen environment. Preliminary results suggest that this system can give at least 20 fold enhancement in volumetric productivity compared to T. brevifolia batch suspension culture at one-half the cost. Phase I research will be focused on testing the technical and economical feasibility of an immobilized taxol reactor, including immobilization efficiency, effect of elicitation on immobilized cells, and stability of immobilized cells in long term operation. Phase II will explore scale-up of the immobilized system capable of producing 7.5 kg taxol/yr. and develop continuous separation process. In Phase III, we will perform full scale production and commercialization of taxol.National Cancer Institute (NCI)