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Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects

Cancer Gene Therapy volume 14, pages 316–326 (2007)Cite this article

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, which selectively induces apoptosis in many transformed cells without apparent toxic side effects in normal tissue. We recently described the construction and characterization of a lentiviral vector for expression of TRAIL. In this report, we evaluate its suitability for therapeutic application. In vitro, we observed specific induction of apoptosis upon transduction in human lung cancer cells. Cell death was partially dependent on successful integration and TRAIL expression by the vectors, but was to some extent mediated by protein carryover, as we found TRAIL protein associated with virus particles. Transduction of subcutaneously growing lung tumors on nude mice with lentiviral TRAIL mediated a transient suppression of tumor growth. Analysis of tumor sections revealed that transduction efficiency of lentiviral control vector but not of lentiviral TRAIL vector was high. This was because of the direct cytotoxic activity of recombinant TRAIL present in viral particles, which prevented efficient tumor transduction. These data therefore suggest that enveloped viral vectors constitutively expressing TRAIL are well suited for ex vivo applications, such as the transduction of tumor-homing cells, but may have a lower effect when used directly for the transduction of tumor cells in vivo.

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Acknowledgements

We thank Peter H Krammer for helpful discussion, Didier Trono for providing lentiviral plasmids, Elisabeth Klimczak, Marlene Roth and Jessica Gabler for excellent technical assistance and the Tumorzentrum Heidelberg for financial support.

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Authors and Affiliations

  1. Research Group Molecular OncoSurgery, Heidelberg, Germany

    T Wenger, J Mattern & I Herr

  2. Centre d'Immunologie de Marseille-Luminy, Marseille, France

    T Wenger

  3. Clinical Cooperation Unit Nuclear Medicine, Heidelberg, Germany

    J Mattern

  4. Division of Apoptosis Regulation, German Cancer Research Center, Heidelberg, Germany

    T L Haas, M R Sprick & H Walczak

  5. Department of Pediatrics, University of Ulm, Ulm, Germany

    K-M Debatin

  6. Department of Surgery, University of Heidelberg, Heidelberg, Germany

    M W Büchler & I Herr

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  1. T Wenger
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Correspondence to I Herr.

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Wenger, T., Mattern, J., Haas, T. et al. Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent and -independent effects. Cancer Gene Ther 14, 316–326 (2007). https://doi.org/10.1038/sj.cgt.7701016

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  • DOI: https://doi.org/10.1038/sj.cgt.7701016

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