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Suicide Genes

Escherichia coli-nitroreductase suicide gene control of human telomerase reverse transcriptase-transduced minor histocompatibility antigen-specific cytotoxic T cells

Bone Marrow Transplantation volume 33, pages 963–967 (2004)Cite this article

Summary:

Adoptive immunotherapy with ex vivo generated cytotoxic T lymphocytes (CTLs) is applied for the treatment of leukemia relapses or viral infections after allogeneic stem cell transplantation. A common problem of adoptive immunotherapy strategies is the ex vivo expansion of the generated T cells to sufficient numbers. CTLs can be efficiently expanded by ectopic expression of the human telomerase gene (hTert). However, hTert transduction may also increase the chance for malignant transformation. Therefore, we explored the feasibility of suicide gene control of ex vivo generated CTLs expanded through the ectopic expression of hTert. To this end, we compared the efficacy of the new Escherichia coli-nitroreductase (E. coli-Ntr) suicide gene with the well-known herpes simplex virus-thymidine kinase (HSV-Tk). Introduction of hTert provided the transduced CTLs with a distinct growth advantage over the nontransduced CTLs. The hTert-E. coli-Ntr double-transduced CTLs retained their antigen-specific functions. Treatment of hTert-E. coli-Ntr double-transduced CTLs with metronidazole significantly inhibited the proliferation to a similar extent to the treatment of hTert-HSV-Tk double-transduced CTLs with ganciclovir. This is the first application of the E. coli-nitroreductase gene for the elimination of human T cells with metronidazole.

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Acknowledgements

This work was supported in part by grants from the Dutch Cancer Society, the Leiden University Medical Center and the European FP5 grant: EU QLRT-2000-01265. We thank Dr L Oosten for help with the IFN-γ measurements and Drs R Offringa and B Wieles for reading the manuscript.

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  1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    R M Verdijk, M Wilke, V Beslier, A Kloosterman, A Brand, E Goulmy & T Mutis

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  1. R M Verdijk
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  2. M Wilke
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  3. V Beslier
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  4. A Kloosterman
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  6. E Goulmy
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Correspondence to E Goulmy.

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Verdijk, R., Wilke, M., Beslier, V. et al. Escherichia coli-nitroreductase suicide gene control of human telomerase reverse transcriptase-transduced minor histocompatibility antigen-specific cytotoxic T cells. Bone Marrow Transplant 33, 963–967 (2004). https://doi.org/10.1038/sj.bmt.1704470

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