SHOT proposes research leading to the commercialization of technology for magnetic isolation of hematopoietic stem cells from human umbilical cord blood, bone marrow and peripheral apheresis product cells. Bone marrow transplantation (BMT) is an established therapy for certain leukemias and other hematologic diseases. The high cure potential of allogeneic BMT is limited by the need for matched histocompatible donors to minimize the possibility of graft-versus-host disease. The ability to isolate stem cells opens a new clinical approach for engineering a most suitable graft. In Phase I research SHOT'S collaborators at The Cleveland Clinic Foundation established that the Quadrupole Magnetic (flow) Sorter (QMS) fulfills most of the requirements for hematologic stem cell selection with its much higher yield and capacity relative to most other methods, and SHOT demonstrated the manufacture of prototype sterile disposable magnetic flow channels and a QMS system. Phase II research thus calls for the design of a package, consisting of an automated QMS facility and disposable channels with sufficient precision, reproducibility and capacity to qualify ultimately for the isolation of human hematopoietic stem cells in the clinical setting. SHOT will (1) perform research to increase the sample size that the QMS system can process from 140 ml to 500 ml; (2) investigate imumunomagnetic labeling technologies to increase the magnetic mobility of the labeled cells, thus increasing sample processing speed; (3) refine the QMS system design in accordance with Current Good Manufacturing Practices (cGMP) design guidelines to incorporate lessons learned, making the system faster, more versatile and more user-friendly; and (4) complete a betatesting program in nationally-known cancer and cell therapy laboratories. The proposed Phase II end items are two pre-market manufactured QMS system prototypes and a set of refined separation channels capable of supporting the beta testing program and ready for the cGMP verification process. SHOT'S goal for the QMS system is the capability of sorting 10 million cells/sec at a total throughput of 8 ml/min or greater with a recovery and purity of 60% or greater. Phase III activities will include manufacture of the QMS systems and separation channels for sale in the research market, as well as a directed effort towards FDA compliance for sales of the QMS systems and separation channels under cGMP in the clinical setting.
