Methods For Positive And Negative Selection Of Hematopoietic Progenitor Cells

造血祖细胞的正向和负向选择方法

基本信息

  • 批准号:
    7733563
  • 负责人:
  • 金额:
    $ 3.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

Preclinical and clinical studies of automated closed systems for positive and negative selection of lymphohematopoietic cells have been done in collaboration with biotechnology firms which have developed systems for potential application to clinical cellular therapies: CellPro T-cell Depletion System: A clinical evaluation of this two-step positive (CD34) and negative (CD2) selection system, which uses an immunoabsorption approach, was completed in August 1998. This study randomized 24 allogeneic donors to fresh versus pooled processing of stem cell apheresis products. Results demonstrated equivalence between the two study arms in processing and clinical outcomes, so the pooled processing approach was used for practical and economic reasons (less processing time, lower costs associated with use of one expensive system versus two). This system is no longer clinically available. A manuscript comparing results of this system with the Nexell Isolex system was published in October 2001 (Nakamura et al. Br J Haematol). Nexell, Inc. Isolex: Studies of the automated Isolex 300i for immunomagnetic selection of hematopoietic progenitor cells were completed. Over 100 selection procedures on version 2.0 (either positive only or combined positive/negative selection) have been completed, and over 100 selection procedures on version 2.5 were completed over the past 3 years. Studies of combined positive + negative selection aimed to achieve maximum T-cell depletion of peripheral blood stem cell products have led to incorporation of this method into several allogeneic transplantation protocols. Results on the version 2.5 combined positive/negative procedure show a mean CD3+ T-cell depletion of 5 logs, with mean CD34+ cell recovery of 60 percent. Evaluation of different T-cell antibodies (CD2 alone vs. CD4+CD8 vs. CD2+CD6+CD7) demonstrated equivalence in the combined positive/negative method. This method will continue to be used in clinical trials. Miltenyi CliniMacs/CD34 positive selection: In FY 2000, we performed a preclinical study of positive selection of normal donor mobilized PBSC using this system. Mean CD34+ cell recovery of 55 percent and a mean CD3+ cell depletion of 5 logs. This system may be incorporated into future clinical trials. Miltenyi CliniMacs/AC133 positive selection: In FY 2002, we initiated a preclinical study, in collaboration with NHBLI/Cardiology Branch, on selection of peripheral blood cells positive for AC133, a newer marker of progenitor cells that includes the angioblastic lineage. Two selection procedures have been done to date. This will be continued into FY2003, and will serve as the foundation for clinical trials of ex vivo generated angioblasts for treatment of coronary artery and myocardial disease. In FY2003, additional AC133 selection studies were performed on the Miltenyi CliniMacs system and plans were made to expand these studies in the coming fiscal year to support cardiology cell therapy initiatives. During FY2006, use of Isolex 300i for immunomagnetic selection for CD34 enrichment was gradually phased out while use of the Miltenyi CliniMACs instrument and microbeads were implemented. The CliniMACs CD34 enrichment procedure allowed for processing higher TNC per product processed and greater log depletion of CD3 cells. Also, Miltenyi manufactured microbeads with specificities for other antigens such that other enrichments and depletion procedures have been evaluated for clinical trial. One example is the CD3 depletion followed by CD56 enrichment to isolate natural killer (NK) cells for ex vivo culture expansion.
用于淋巴造血细胞阳性和阴性选择的自动封闭系统的临床前和临床研究已经与生物技术公司合作完成,这些公司已经开发了用于临床细胞治疗的潜在应用系统:CellPro t细胞消耗系统:1998年8月完成了对这种两步阳性(CD34)和阴性(CD2)选择系统的临床评估,该系统使用免疫吸收方法。本研究将24名异体供体随机分配到新鲜的干细胞分离产品和混合处理的干细胞分离产品。结果表明,两个研究组在处理和临床结果方面是等效的,因此出于实际和经济原因,采用了合并处理方法(处理时间更短,使用一种昂贵的系统比使用两种系统成本更低)。该系统已不再临床可用。将该系统与Nexell Isolex系统的结果进行比较的手稿发表于2001年10月(Nakamura et al.)。[J]。Nexell公司。Isolex:完成了用于造血祖细胞免疫磁选择的自动Isolex 300i的研究。在2.0版本上已经完成了100多个选择程序(要么是正面选择,要么是正面/负面组合选择),在过去3年里,在2.5版本上完成了100多个选择程序。为了最大限度地消耗外周血干细胞产品的t细胞,联合阳性+阴性选择的研究已经将这种方法纳入了几种同种异体移植方案中。2.5版本联合阳性/阴性程序的结果显示,CD3+ t细胞平均耗损5 log, CD34+细胞平均回收率为60%。评估不同的t细胞抗体(CD2单独、CD4+CD8、CD2+CD6+CD7)在联合阳性/阴性方法中证明是等效的。该方法将继续用于临床试验。Miltenyi CliniMacs/CD34阳性选择:在2000财年,我们使用该系统进行了正常供体动员PBSC阳性选择的临床前研究。平均CD34+细胞回收率为55%,平均CD3+细胞损耗为5 log。该系统可纳入未来的临床试验。Miltenyi CliniMacs/AC133阳性选择:在2002财年,我们与NHBLI/心脏病学分支合作,启动了一项临床前研究,选择AC133阳性的外周血细胞,AC133是一种新的祖细胞标记物,包括成血管细胞谱系。迄今为止已经进行了两次选择程序。这项工作将持续到2003财年,并将作为体外生成的成血管细胞用于治疗冠状动脉和心肌疾病的临床试验的基础。2003财年,在Miltenyi CliniMacs系统上进行了额外的AC133选择研究,并计划在下一财年扩大这些研究,以支持心脏病细胞治疗计划。在2006财年,使用Isolex 300i进行CD34富集的免疫磁选逐渐被淘汰,同时开始使用Miltenyi CliniMACs仪器和微珠。CliniMACs CD34富集程序允许处理更高的每个处理产品的TNC和更大的CD3细胞的对数损耗。此外,Miltenyi制造的微珠具有其他抗原的特异性,因此其他富集和消耗程序已被评估用于临床试验。一个例子是CD3耗尽后CD56富集,分离自然杀伤细胞(NK)进行体外培养扩增。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies.
CD34 细胞剂量可预测血液恶性肿瘤 T 细胞耗尽 HLA 一致造血干细胞移植 (HSCT) 后的复发和生存。
  • DOI:
    10.1046/j.1365-2141.2000.01838.x
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    6.5
  • 作者:
    Bahceci,E;Read,EJ;Leitman,S;Childs,R;Dunbar,C;Young,NS;Barrett,AJ
  • 通讯作者:
    Barrett,AJ
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David Stroncek其他文献

David Stroncek的其他文献

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{{ truncateString('David Stroncek', 18)}}的其他基金

Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    10471695
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    9154063
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    9986421
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Develop novel assays for assessing cellular and gene therapies
开发评估细胞和基因疗法的新方法
  • 批准号:
    10913195
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    9340948
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    8565300
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Structure and Function Granulocyte Antigens
粒细胞抗原的结构和功能
  • 批准号:
    8952804
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Development of novel cell and gene therapies
新型细胞和基因疗法的开发
  • 批准号:
    10265869
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Structure and Function Granulocyte Antigens
粒细胞抗原的结构和功能
  • 批准号:
    9154059
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:
Develop novel assays for assessing cellular and gene therapies
开发评估细胞和基因疗法的新方法
  • 批准号:
    10672072
  • 财政年份:
  • 资助金额:
    $ 3.94万
  • 项目类别:

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Molecular regulation of angioblast migration during cornea development
角膜发育过程中成血管细胞迁移的分子调控
  • 批准号:
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  • 财政年份:
    2012
  • 资助金额:
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  • 项目类别:
Molecular regulation of angioblast migration during cornea development
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角膜发育过程中成血管细胞迁移的分子调控
  • 批准号:
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  • 财政年份:
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