This Small Business Innovation Research Phase I project states that the use of autologous hematopoietic stem cell (HSC) transplantation is increasing for treatment of many cancers. However, tumor cell contamination within harvested HSC products continues to be of major concern. Contaminating tumor cells are known to contribute to cancer relapse, based on studies using genetically-marked transplanted cells. Several purging methods have been developed, but all leave detectable tumor cells in the transplant. Furthermore, existing methods reduce HSC numbers, compromising the therapeutic value of purging. Therefore, technology that reliably eliminates detectable tumor cells from a transplant, while leaving HSCs undamaged, is needed. This proposal describes a patented innovative approach integrating fluorescence scanning cytometry, real-time image analysis, and laser ablation. Phase I studies are proposed to evaluate feasibility of an approach that would accelerate the process to the speed required for clinical-scale operation. A breadboard optical system will be assembled and tested for rapid scanning and identification of fluorescent targets. Successful Phase I results will lead to Phase II studies to fully develop the prototype instrument and initiate clinical trials. This will lead to commercialization of a method to eliminate tumor cells from an HSC transplant within a several hour automated procedure. Over 30,000 autologous HSC transplants were performed in 1997, and the number is increasing 20-25% per year. The resulting instrumentation is applicable to any process that requires a highly defined cell product.
