Recent advances in cell separation and in vitro expansion and gene transfer technologies have created new opportunities for therapeutic intervention in HIV-1 infection. These include the ability to expand T- cell populations and/or to purify highly enriched hematopoietic progenitor populations for the purposes of immunologic or hematologic reconstitution. The handling of HIV-1 infected cells for therapeutic purposes requires the ability to manipulate large volumes of patient- derived material such as leukaphoresis products in a biosafety level 3 (BSL3) facility. Cell expansion and large scale stem cell purification, using suitable 'manufacturing' precautions for re-infusion into patients requires highly trained technical personnel, as well as sophisticated equipment not usually available to most investigators. Therefore, we will to develop a core BSL3 stem cell procurement/T-cell expansion facility to function in support of clinical trials and basic research at UCLA. This facility would prepare and expand highly purified stem cell or T-cell populations from leukapheresis products or bone marrow of HIV-1-infected individuals for both therapeutic and research purposes. The facility will also provide logistical support for large scale gene transfer involving RAC/FDA approved vectors into T-cells/stem cells for therapeutic purposes. Faculty from the UCLA Departments of Medicine (Division of Hematology- Oncology), Infectious Diseases, Microbiology & Immunology, and others engaged in clinical basic research requiring T-cells or stem cells from controls and HIV-1-infected individuals will directly benefit from this facility. The core facility will support ongoing cytotoxic T-cell expansion trials in AIDS, transplantation trials in HIV-1-related lymphoma, and institutional and regional gene therapy protocols, using RA C/FDA-approved vectors as they became available. It will develop novel T-cell expansion protocols using newer cytokines and separation techniques. The facility will test and assimilate new cell separation technologies, including gene transfer technologies, as they evolve for both therapeutic and scientific purposes. The core will also support basic science studies of HIV-1-specific cytotoxic T-cell populations, stem cell transplantation into SCID mice, for testing of gene therapy strategies.
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