1. ¹Research Group Molecular OncoSurgery, Heidelberg, Germany
2. ²Centre d'Immunologie de Marseille-Luminy, Marseille, France
3. ³Clinical Cooperation Unit Nuclear Medicine, Heidelberg, Germany
4. ⁴Division of Apoptosis Regulation, German Cancer Research Center, Heidelberg, Germany
5. ⁵Department of Pediatrics, University of Ulm, Ulm, Germany
6. ⁶Department of Surgery, University of Heidelberg, Heidelberg, Germany

Correspondence: Professor I Herr, Department of Surgery, Molecular OncoSurgery Group, University of Heidelberg, Im Neuenheimer Feld 365, 69120 Heidelberg, Germany. E-mail: i.herr@dkfz.de

Received 23 May 2006; Revised 20 August 2006; Accepted 9 October 2006; Published online 22 December 2006.

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.