Magnetic Sorter Channels for Stem Cells

描述(由申请人提供)：Shot提出了一项研究，旨在将从人脐血、骨髓和外周血液分离产品细胞中磁分离造血干细胞的技术商业化。骨髓移植(BMT)是治疗某些白血病和其他血液病的既定疗法。异基因骨髓移植的高治愈潜力受到匹配组织相容供者的需求的限制，以将移植物抗宿主病的可能性降至最低。分离干细胞的能力为设计最合适的移植物开辟了一条新的临床途径。在第一阶段的研究中，Sort在克利夫兰临床基金会的合作者证实，四极磁(FLOW)分选器(QMS)与大多数其他方法相比，以其更高的产量和容量满足了血液干细胞选择的大部分要求，并展示了无菌一次性磁性流动通道和QMS系统的原型制造。因此，第二阶段的研究需要设计一套由自动化QMS设施和具有足够精度、重复性和能力的一次性通道组成的一揽子方案，最终有资格在临床环境中分离人类造血干细胞。Shoot将(1)开展研究，将QMS系统可处理的样本量从140毫升增加到500毫升；(2)研究免疫磁标记技术，以增加标记细胞的磁性迁移率，从而提高样本处理速度；(3)根据当前的良好制造规范(CGMP)设计指南，改进QMS系统设计，以吸取经验教训，使系统更快、更通用、更人性化；以及(4)在全国知名的癌症和细胞治疗实验室完成一项测试计划。拟议的第二阶段最终产品是两个上市前生产的QMS系统原型和一套能够支持Beta测试计划并为cGMP验证过程做好准备的精细化分离通道。Sort的QMS系统的目标是能够以8毫升/分钟或更高的总吞吐量分选1000万个细胞/秒，回收率和纯度为60%或更高。第三阶段的活动将包括制造QMS系统和在研究市场销售的分离通道，以及有针对性地努力在临床环境下按照美国食品和药物管理局的要求在cGMP下销售QMS系统和分离通道。

DESCRIPTION (provided by applicant): 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.