Use of autologous hematopoietic stem cell (HSC) transplantation is increasing for treatment of many cancers. However, tumor cell contamination within harvested HSC products is 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 scanntng cytometry, real- time image analysis, and laser ablation. Phase I studies are proposed to select appropriate anti-cancer antibodies based upon screening against many tumor cell lines. Fluorescent detection of tumor cells will be optimized using image enhancement software algorithms with a high performance cooled-CCD camera. Successful Phase I results will lead to Phase II studies to test contaminated patient HSC specimens, and further develop the reagents and plastic disposables required to implement clinical trials with the beta-prototype Photosis(TM) instrument being developed. This will lead to commercialization of a method to eliminate tumor cells from an HSC transplant within a several hour automated procedure.
These studies will lead to commercialization of a method to eliminate detectable tumor cells from an HSC transplant within a several hour automated procedure. In 1996, over 40,000 HSC transplants were performed worldwide, and the number is increasing 20-25% per year. The resulting instrumentation could ultimately be applicable to any process that requires a highly defined cell product.
