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A novel ‘sort-suicide’ fusion gene vector for T cell manipulation

Gene Therapy volume 9, pages 1633–1638 (2002)Cite this article

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.

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Acknowledgements

The authors wish to thank Dung Ung and Melanie Engel for excellent technical assistance, as well as the blood bank of the University Hospital Eppendorf for kind cooperation. We are indebted to Francis Ayuk for critical reading of the manuscript. This work was supported by the European Community (QLK3-2001-01265). AW is supported by the Deutsches Krebsforschungszentrum (Ca 97).

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Authors and Affiliations

  1. Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany

    B Fehse, O S Kustikova, A Wahlers & A R Zander

  2. Department of Cell and Virus Genetics, Heinrich-Pette-Institute, Hamburg, Germany

    O S Kustikova, Z Li, A Wahlers, W R Beyer & C Baum

  3. Department of Hematology and Oncology, Experimental Cell Therapy, Medical School Hannover, Germany

    Z Li & C Baum

  4. Department of Tumor Virology, Heinrich-Pette-Institute, Hamburg, Germany

    W Bohn

  5. INSERM E-0119/UPRES EA-2284, Etablissement Français du Sang-Bourgogne/Franche-Comté, Besançon, France

    D Chalmers & P Tiberghien

  6. EUFETS AG Idar-Oberstein, Germany

    K Kühlcke

Authors
  1. B Fehse
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  2. O S Kustikova
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  3. Z Li
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  4. A Wahlers
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  6. W R Beyer
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  7. D Chalmers
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  8. P Tiberghien
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  9. K Kühlcke
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  10. A R Zander
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  11. C Baum
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Fehse, B., Kustikova, O., Li, Z. et al. A novel ‘sort-suicide’ fusion gene vector for T cell manipulation. Gene Ther 9, 1633–1638 (2002). https://doi.org/10.1038/sj.gt.3301828

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  • DOI: https://doi.org/10.1038/sj.gt.3301828

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