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.
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