THE FUTURE OF CELL THERAPY

Peripheral blood has replaced bone marrow as a source of hematopoietic stem cells for autologous rescue after high-dose chemotherapy. Patien ts who receive peripheral blood stem cell (PBSC) transplants experienc e rapid and sustained hematopoietic reconstitution. As a result, trans plant-related mortality is now less than 5% at many centers, and the c ost of high-dose chemotherapy has decreased considerably. However, the relapse rate continues to be unacceptably high, and the collection of hematopoietic stem cells from peripheral blood is inconvenient, time consuming, and expensive. This article discusses the current status of novel technologies such as positive selection of hematopoietic stem c ells, ex vivo expansion of hematopoietic progenitor cells, allogeneic PBSC transplants, and umbilical cord blood transplants. Several compan ies are actively developing devices that positively select hematopoiet ic stem cells. Because positive selection reduces the volume of infuse d cells, patients experience fewer adverse effects related to dimethyl sulfoxide (DMSO) or lysed cells. These devices may also serve as an ex vivo method to remove (''purge'') residual tumor cells. Positively se lected hematopoietic stem cells may be expanded ex vivo to produce a l arge number of a specific population of hematopoietic cells. By adding cytokines that stimulate and activate lymphocytes, natural killer cel ls, and other immune effector cells, investigators could expand the nu mber of immune effector cells with antitumor activity and then infuse them into patients as a form of adaptive immunotherapy. Finally, perip heral blood and umbilical cord blood are promising new sources of hema topoietic stem cells for allogeneic transplants.