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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项初步研究，旨在确定慢病毒转导的造血祖细胞(HPC)表达的以RNA为基础的抗HIV治疗在接受自体干细胞移植(HCT)治疗中高度恶性艾滋病患者中的安全性和可行性。慢病毒载体编码3种形式的抗HIV RNA：针对HIV-1 TAT/rev(SHI)外显子的短发夹状RNA(ShRNA)，针对HIV TAT反应元件(TAR)的诱饵，以及靶向宿主细胞CCR5细胞因子受体(CCR5RZ)的核酶。该载体用于转导CD34选择的自体HPC，命名为rHIV7-SHI-TAR-CCR5RZ，将由位于希望之城的贝克曼研究所生产。在标准的HPC动员和分离收集(HPC-A)之后，一部分细胞将被冷冻保存，但不进行处理以供以后用作治疗，一部分将使用Miltenyi CliniMax系统进行CD34细胞的浓缩，冷冻保存后通过感染rHIV7-SHI-TAR-CCR5RZ进行转基因。受试者接受卡莫司汀(BCNU)、依托泊苷(VP16)和环磷酰胺的预适应治疗，在自体移植(HCT)时，输注转导的HIV7-SHI-TAR-CCR5RZ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 CliniMax 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.