Long-term regulation of genetically modified primary @entity1583 cells in XXXX .

@entity235 @entity16130 @entity16131 @entity1583 @entity16129
We report long-term results from a large animal model of in vivo selection. Nine years ago, we transplanted two @entity235 (E900 and E958) with autologous marrow @entity16129 (+) cells that had been transduced with a gammaretrovirus vector encoding a conditionally activatable derivative of the thrombopoietin receptor. Receptor activation through administration of a chemical inducer of dimerization (CID) ( @entity16130 or @entity16131 ) confers a growth advantage. We previously reported responses to two 30-day intravenous (i.v.) courses of @entity16130 administered within the first 8 months post-transplantation. We now report responses to 5-day subcutaneous (s.c.) courses of @entity16130 or @entity16131 at months 14, 90, and 93 (E900), or month 18 (E958), after transplantation. Long-term monitoring showed no rise in transduced cells in the absence of drug. Retroviral insertion site analysis showed that 4 of 6 (E958) and 5 of 12 (E900) transduced @entity1583 cell clones persisted lifelong. Both @entity235 were euthanized for reasons unrelated to the gene therapy treatment at 8 years 11 months (E958) and 11 years 1 month (E900) of age. Three clones from E900 remained detectable in each of two secondary recipients, one of which was treated with, and responded to, @entity16131 . Our results demonstrate the feasibility of safely regulating genetically engineered @entity1583 cells over many years.
