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

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。 这是一项初步研究，以确定在接受自体干细胞移植（HCT）治疗中高度恶性艾滋病淋巴瘤的患者中，慢病毒转导的造血祖细胞（HPC）中表达的基于RNA的抗HIV治疗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：靶向HIV-1达特/rev（shI）外显子的短发夹RNA（shRNA）形式的RNAi、HIV TAT反应元件（TAR）的诱饵和靶向宿主细胞CCR 5细胞因子受体（CCR 5 RZ）的核酶。这种载体被称为rHIV 7-shI-TAR-CCR 5 RZ，将由位于City of Hope的贝克曼研究所生产。在HPC标准动员和单采（HPC-A）采集后，将一部分细胞冻存，但不进行其他操作，以供后续治疗使用，并将一部分细胞使用Miltenyi CliniMacs系统富集CD 34+细胞，冻存，随后通过rHIV 7-shI-TAR-CCR 5 RZ感染进行遗传修饰。受试者将接受卡莫司汀（BCNU）、依托泊苷（VP 16）和环磷酰胺的预处理治疗，并在自体移植（HCT）时输注rHIV 7-shI-TAR-CCR 5 RZ转导的细胞，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.