Our work has focused on bringing techniques developed in our laboratory for retroviral gene transfer into hematopoietic stem cells to clinical application. We have shown that clinical-grade retroviral supernatants can efficiently infect both bone marrow and peripheral blood hematopoietic progenitor cells and long-term culture initiating cells as assayed in vitro. We have worked with cells enriched for progenitor and stem cell activity by immunoselection for the CD34 antigen: these enriched populations offer practical and theoretical advantages as targets for gene therapy. Based on this preclinical experience, we received RAC approval for three clinical gene marking protocols incorporated into autologous stem cell transplantation protocols for multiple myeloma, chronic myeloid leukemia, and breast cancer. We have begun a successful autologous transplantation program on the NHLBI inpatient ward, and we will begin the gene marking phase of the protocols in late summer 1992. These protocols should answer important questions regarding feasibility of gene transfer to stem cells, characteristics of autologous engraftment from bone marrow versus peripheral blood sources, and mechanisms of relapse post- transplantation. We are currently developing therapeutic vectors for all three diseases that will go forward into clinical protocols once adequate preclinical data has been obtained. We have also developed an amendment to the human ADA gene therapy protocol involving peripheral blood stem cells in hopes of curing children with SCIDS with one gene-corrected cell infusion instead of multiple T-cell infusions.
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