CLINICAL TRIAL: TRANSDUCTION OF CD34+ CELLS FROM THE UMBILICAL CORD BLOOD OF INF

临床试验：从 INF 脐带血转导 CD34 细胞

• 批准号: 7982050
• 负责人: Donald B Kohn
• 金额: $ 15.65万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7982050
• 关键词: Bone Marrow; CD34 gene; Cells; Child; Clinical Research; Clinical Trials; Complementary DNA; Computer Retrieval of Information on Scientific Projects Database; Effectiveness; Engraftment; Funding; Gene Transfer Techniques; Genes; Grant; Hematopoietic stem cells; Human; Immunity; Infant; Institution; Marrow; Mature T-Lymphocyte; Patients; Production; Research; Research Personnel; Resources; Retroviral Vector; Safety; Source; T-Lymphocyte; Testing; Umbilical Cord Blood; United States National Institutes of Health; enzyme activity; gene correction; immune function; pegademase bovine; reconstitution; retroviral-mediated

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypothesis of this proposal is: Retroviral-mediated transfer of a normal human ADA cDNA into CD34+ hematopoietic stem cells of infants and children with ADA-deficient SCID, who have undergone marrow cytoreduction and are not on PEG-ADA replacement, can be performed safely and will result in the production of mature T lymphocytes, expressing ADA enzyme activity and restoring immune function. In all, these clinical studies will determine the safety and effectiveness of current retroviral-mediated gene transfer techniques to introduce genes into human hematopoietic stem cells from the bone marrow. Two different retroviral vectors, GCsap-M-ADA and MND-ADA, will be compared for their abilities to express the human ADA cDNA and confer a selective survival advantage upon T lymphocytes. Marrow cytoreduction in the absence of PEG-ADA will be tested, to assess the safety of the approach and its effect on engraftment and selective survival of gene-corrected cells. Additionally, the specific benefits for reconstitution of immunity in ADA-deficient SCID patients will be assessed.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这一建议的核心假设是： 逆转录病毒介导的正常人ADA cDNA转移到ADA缺陷型SCID婴儿和儿童的CD 34+造血干细胞中，这些婴儿和儿童接受了骨髓细胞减少术，未接受PEG-ADA替代，可以安全地进行，并将导致成熟T淋巴细胞的产生，表达ADA酶活性并恢复免疫功能。 总之，这些临床研究将确定目前逆转录病毒介导的基因转移技术的安全性和有效性，将基因从骨髓导入人类造血干细胞。 将比较两种不同的逆转录病毒载体GCsap-M-ADA和MND-ADA表达人ADA cDNA并赋予T淋巴细胞选择性生存优势的能力。 将在不存在PEG-ADA的情况下测试骨髓细胞减少，以评估该方法的安全性及其对基因校正细胞的植入和选择性存活的影响。 此外，还将评估ADA缺陷型SCID患者免疫重建的具体获益。