High Performance Magnetic Cell Sorting

高性能磁性细胞分选

• 批准号: 6902639
• 负责人: JEFFREY John CHALMERS
• 金额: $ 54万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-21 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6902639
• 关键词: CD34 molecule; T lymphocyte; biomedical equipment development; biotechnology; cell sorting; clinical biomedical equipment; clinical research; colony stimulating factor; hematopoietic stem cells; hematopoietic tissue transplantation; high throughput technology; homologous transplantation; human subject; immunomagnetic separation; leukocyte depletion therapy; mass tissue /cell culture; natural killer cells

DESCRIPTION (provided by the applicant): An area of increasing interest, and potentially significant clinical use, is performing mismatched stem cell transplants for high-risk and refractory hematological malignancies using related donors. Such patients currently undergo transplants using HLA matched sibling or unrelated donor stem cells. Using haplotype-mismatched donors from siblings, parents or children would permit the availability of suitable donors for more than 90-95% of candidate patients. However, the main limitation is graft-versus-host disease (GVHD). GVHD can be almost eliminated by extensive T-cell depletion (>5 logs). While T cell depletion increases the risk of graft rejection, this can be overcome by the use of very large doses of stem cells. Therefore, it is desirable to have a system where very large numbers of stem cells can be efficiently processed to deplete T-cells, and with minimal loss of these stem cells. A second area of increasing interest, and potentially significant clinical use, is the isolation of Natural Killer (NK) Cells for Immunotherapy. NK cells are important cells of the innate immune system that are not involved in specific antigen recognition. These cells are important in the defense against infections, but also have potent anti-tumor effects. Currently, there is growing interest in the use of both autologous and allogeneic activated NK cells for cancer immunotherapy. In particular, the use of allogeneic NK cells mismatched for HLA-C alleles of the recipient can exert very potent anti-leukemic effect in vitro. Infusion of NK cells may also assist engraftment of stem cells in the bone marrow transplant setting. This project will focus on the development/application of a high throughput, flow through immunomagnetic cell separation system currently under development for clinical scale T-cell depletion and NK isolation. While several systems have been developed, none are currently approved for these indications, and their performance is generally suboptimal. With respect to the recovery of stem cells during T-cell depletion, a significant increase in stem cell recovery is needed, from reported mean values of 41 to over 80%, to facilitate 'mega-dose' CD34 cell therapy in mismatched transplants. Less research has been carried out for clinical scale NK cell separation technology, with current methods performing sub-optimally due to loss of over 50% of the NK cells. Specifically, therefore, our objectives are: 1.To demonstrate significantly superior performance for T-cell depletion with the aim of achieving 5 log10 depletion of T cells, with >90% recovery of CD34+ cells in greater than or equal too 80% of clinical apheresis samples obtained from normal donors. 2. To demonstrate significantly superior performance of NK cell isolation with the aim of isolating CD56+ CD3- NK cells with > 90% recovery and with <1 x 10/5 CD3+ cell contamination in greater than or equal to 90% of peripheral blood apheresis products processed.

描述（由申请人提供）：使用相关供体对高风险和难治性血液系统恶性肿瘤进行错配干细胞移植是一个越来越受关注的领域，并且具有潜在的重要临床应用。这类患者目前使用HLA匹配的兄弟或非亲属供体干细胞进行移植。使用来自兄弟姐妹、父母或子女的单倍型不匹配的供体，可以为超过90-95%的候选患者提供合适的供体。然而，主要的限制是移植物抗宿主病（GVHD）。GVHD几乎可以通过广泛的t细胞消耗（bbb50 log）来消除。虽然T细胞耗竭会增加移植排斥反应的风险，但这可以通过使用非常大剂量的干细胞来克服。因此，我们希望有一个系统，在这个系统中，大量的干细胞可以被有效地处理以消耗t细胞，并且这些干细胞的损失最小。