A PILOT STUDY OF SAFETY AND FEASIBILITY OF STEM CELL THERAPY FOR AIDS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这是一项初步研究，旨在确定在接受自体干细胞移植（HCT）治疗中度和高度恶性艾滋病淋巴瘤的患者中，在慢病毒转导的造血祖细胞（HPC）中表达的基于RNA的抗HIV疗法的基因转移的安全性和可行性。慢病毒载体编码 3 种形式的抗 HIV RNA：针对 HIV-1 tat/rev (shI) 外显子的短发夹 RNA (shRNA) 形式的 RNAi、HIV TAT 反应元件 (TAR) 的诱饵以及针对宿主细胞 CCR5 细胞因子受体 (CCR5RZ) 的核酶。该载体用于转导自体 CD34 选择的 HPC，称为 rHIV7-shI-TAR-CCR5RZ，将由希望之城的贝克曼研究所生产。在标准 HPC 动员和单采术 (HPC-A) 收集后，一部分细胞将被冷冻保存，但不进行任何操作以供以后用作治疗，一部分细胞将使用 Miltenyi CliniMacs 系统富集 CD34+ 细胞，冷冻保存，然后通过感染 rHIV7-shI-TAR-CCR5RZ 进行基因修饰。受试者将接受卡莫司汀（BCNU）、依托泊苷（VP16）和环磷酰胺的调理治疗，并在自体移植（HCT）时输注rHIV7-shI-TAR-CCR5RZ转导细胞，然后24小时后输注未转导的自体HPC-A。

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. This is a pilot study to determine the safety and feasibility of gene transfer of RNA-based anti-HIV therapy expressed in lentivirus-transduced hematopoietic progenitor cells (HPC) in patients undergoing autologous stem cell transplantation (HCT) for intermediate and high grade AIDS lymphoma. The lentivirus vector encodes 3 forms of anti-HIV RNA: RNAi in the form of a short hairpin RNA (shRNA) targeted to an exon in HIV-1 tat/rev (shI), a decoy for the HIV TAT-reactive element (TAR) and a ribozyme that targets the host cell CCR5 cytokine receptor (CCR5RZ) . The vector, used to transduce autologous CD34-selected HPC, is called rHIV7-shI-TAR-CCR5RZ and will be produced by the Beckman Research Institute at City of Hope. Following standard mobilization of HPC and collection by apheresis (HPC-A), a portion of the cells will be cryopreserved but otherwise unmanipulated for later use as treatment and a portion will be enriched for CD34+ cells using a Miltenyi CliniMacs system, cryopreserved and later genetically modified by infection with rHIV7-shI-TAR-CCR5RZ. The subjects will undergo conditioning therapy using carmustine (BCNU), etoposide (VP16) and cyclophosphamide, and at the time of autologous transplantation (HCT), the rHIV7-shI-TAR-CCR5RZ transduced cells will be infused and then 24 hours later, the untransduced autologous HPC-A will be infused.