Abstract
We propose to conduct a Phase I Clinical Trial to apply the techniques of gene therapy to the treatment of HIV infection. It is a twin donor study, with one individual HIV super(+), the other HIV super(-) using a sample size of 4-6 pairs of HLA-identical twins. The study procedures will comprise one round of leukapheresis from the HIV super(-) twin followed by CD4 super(+) T lymphocyte isolation, retoviral transduction, cell expansion and infusion into the HIV super(+) twin. The harvested peripheral blood lymphocytes (PBLs) will be activated using OKT3 and IL-2, divided into two equal groups, and transduced with a replication-incompetent vector containing a neomycin-resistance gene (neo super(R)) or a vector containing a neo super(R)/ribozyme gene. The two cell populations will then be separately expanded with IL-2. These ex vivo procedures will all occur with a 'CellMax super(TM) Artificial Capillary Cell Culture System'. Both populations will then be infused into the HIV super(+) twin (approximately 10 super(9) CD4 super(+) T cells of each neo super(R) only and neo super(R)/ribozyme). Detection of the genetically marked cells (both integration and expression) will be via polymerase chain reaction (PCR) techniques. Frequent monitoring of the recipients will continue for a period of at least 24 weeks post-infusion and will continue indefinitely at regular intervals for assessment of the long-term safety of the procedure. This work is based on previous gene therapy protocols in the adenosine deaminase deficiency and HIV therapeutics areas. In addition, other clinical protocols, conducted in the USA have recently shown persistence, implying proliferation, of HIV super(-) T lymphocytes following infusion into HIV super(+) matched siblings.