title: A novel 'sort-suicide' fusion gene vector for T cell manipulation.
abstract: Retroviral suicide gene vectors have successfully been used in clinical studies to improve the safety of adoptive immunotherapy with allogeneic T lymphocytes in the treatment of malignant and viral diseases. At the same time these studies have revealed several problems that are yet to be resolved including impaired T cell function due to long ex vivo culture. Here we present new retroviral vectors co-expressing truncated CD34, a gene transfer marker which ensures rapid enrichment of transduced cells using commercially available GMP-approved devices, and a splice-corrected variant of Herpes simplex virus thymidine kinase (scHSVtk) which confers high sensitivity to the prodrug ganciclovir. We show that a retroviral hybrid vector, MP71, based on the myeloproliferative sarcoma virus (MPSV) and the murine embryonic stem cell virus (MESV), encoding a tCD34/scHSVtk fusion protein mediates high expression of the 'sort-suicide' selection marker, thereby allowing for highly efficient purification and selective elimination of transduced cells.
authors.affiliation: Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Fehse
authors.forename: O S
authors.initials: OS
authors.lastname: Kustikova
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Wahlers
authors.forename: W
authors.initials: W
authors.lastname: Bohn
authors.forename: W R
authors.initials: WR
authors.lastname: Beyer
authors.forename: D
authors.initials: D
authors.lastname: Chalmers
authors.forename: P
authors.initials: P
authors.lastname: Tiberghien
authors.forename: K
authors.initials: K
authors.lastname: Kühlcke
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
authors.forename: C
authors.initials: C
authors.lastname: Baum
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology; D005819:Genetic Markers; D005822:Genetic Vectors; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019169:Jurkat Cells; D008212:Lymphocyte Depletion / Q000379:methods*; D018613:Microscopy, Confocal; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000637:transplantation*; D014161:Transduction, Genetic
chemical_list: D018952:Antigens, CD34; D005819:Genetic Markers; D015774:Ganciclovir