A novel 'sort-suicide' fusion gene vector for T cell manipulation
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A novel 'sort-suicide' fusion gene vector for T cell manipulation. / Fehse, B; Kustikova, O S; Li, Z; Wahlers, A; Bohn, W; Beyer, W R; Chalmers, D; Tiberghien, P; Kühlcke, K; Zander, A R; Baum, C.
in: GENE THER, Jahrgang 9, Nr. 23, 12.2002, S. 1633-1638.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Kurzpublikation › Forschung › Begutachtung
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TY - JOUR
T1 - A novel 'sort-suicide' fusion gene vector for T cell manipulation
AU - Fehse, B
AU - Kustikova, O S
AU - Li, Z
AU - Wahlers, A
AU - Bohn, W
AU - Beyer, W R
AU - Chalmers, D
AU - Tiberghien, P
AU - Kühlcke, K
AU - Zander, A R
AU - Baum, C
PY - 2002/12
Y1 - 2002/12
N2 - 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.
AB - 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.
KW - Antigens, CD34/genetics
KW - Ganciclovir/pharmacology
KW - Genetic Markers
KW - Genetic Vectors
KW - Humans
KW - Immunotherapy, Adoptive/methods
KW - Jurkat Cells
KW - Lymphocyte Depletion/methods
KW - Microscopy, Confocal
KW - Retroviridae/genetics
KW - T-Lymphocytes/drug effects
KW - Transduction, Genetic
U2 - 10.1038/sj.gt.3301828
DO - 10.1038/sj.gt.3301828
M3 - Short publication
C2 - 12424616
VL - 9
SP - 1633
EP - 1638
JO - GENE THER
JF - GENE THER
SN - 0969-7128
IS - 23
ER -