RAPID COMMUNICATION Myelosuppressive Conditioning Improves Autologous Engraftment of Genetically Marked Hematopoietic Repopulating Cells in Dogs

We have studied the role of different conditioning regimens for engraftment of genetically marked hematopoietic repopulating cells in dogs. Peripheral blood (PB) and/or marrow cells collected after treatment with recombinant canine stem cell factor (rcSCF) or cyclophosphamide were transduced in a vector-containing long-term culture system. Three different vector-producing cell lines with similar viral titers were used. In two of them, the neo-containing LN vector was packaged either in the PA317 cell line with an amphotropic murine retrovirus envelope or the PG13 cell line with the gibbon ape leukemia virus (GALV) envelope. The MFG/GC vector produced in PA317 cells contained the human glucocerebrosidase gene. Nineteen dogs received either no conditioning (group A, n = 5). irradiation to both humeri with 1,000 cGy (group B, n = 51, a sublethal dose of cyclophosphamide 40 mg/kg (group C, n = 4). a sublethal dose of 200 or 300 cGy total body irradiation (TB11 (group D, n = 3). or an otherwise lethal dose of 920 cGy TB1 (group E, n = 3) before intravenous (groups A, C, D, E) or intramedullary (group B) infusion of the transduced autologous hematopoietic cells. Transduction efficiency of hematopoietic cells at the time of infusion into the animals was similar among the