title: Canine T cells transduced with a herpes simplex virus thymidine kinase gene: a model to study effects on engraftment and control of graft-versus-host disease.
abstract: BACKGROUND
  Alloreactive donor T cells in marrow grafts mediate graft-versus-host disease (GVHD), but T-cell depletion has resulted in increased graft failure. Add-back of gene-modified alloreactive donor T cells could prevent graft rejection. After engraftment, in vivo depletion of those modified T cells with ganciclovir may control GVHD.
  
  
  METHODS
  Canine recipient-specific donor cytotoxic T lymphocytes (CTL) were retrovirally transduced with the herpes simplex virus thymidine kinase gene.
  
  
  RESULTS
  Gibbon ape leukemia virus-pseudotyped vector yielded primary CTL transduction efficiency of 22.9+/-9.9%. After selection and expansion, 96.7+/-0.8% of CTL expressed retrovirally transferred genes. Recipient-specific cytotoxic activity was maintained with 84.3% specific lysis. After ganciclovir treatment, herpes simplex virus thymidine kinase-transduced CTL proliferation was reduced 98.7+/-0.2% compared with controls.
  
  
  CONCLUSIONS
  We have demonstrated efficient ex vivo transduction, expansion, maintenance of alloreactivity, and ganciclovir-mediated ablation of canine CTL, which will permit in vivo studies in the dog, a well-established model for GVHD and engraftment.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Georges
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: M W
authors.initials: MW
authors.lastname: Brunvand
authors.forename: H P
authors.initials: HP
authors.lastname: Kiem
authors.forename: P F
authors.initials: PF
authors.lastname: Moore
authors.forename: P
authors.initials: P
authors.lastname: Malik
authors.forename: D
authors.initials: D
authors.lastname: Ennist
authors.forename: R A
authors.initials: RA
authors.lastname: Nash
mesh_terms: D000818:Animals; D004285:Dogs; D018139:Simplexvirus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D013937:Thymidine Kinase