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Using lentiviral vectors for efficient pancreatic cancer gene therapy

Cancer Gene Therapy volume 17, pages 315–324 (2010)Cite this article

Abstract

Pancreatic cancer (PC) remains a life-threatening disease. Efficient therapeutic gene delivery to PC-derived cells continues to present challenges. We used self-inactivated lentiviral vectors to transduce PC-derived cells in vitro and in vivo. We showed that lentiviral vectors transduce PC-derived cell lines with high efficiency (>90%), regardless of the differentiation state of the cell. Next, we transferred human interferon beta (hIFN-β) gene. Expression of hIFN-β in PC cells using lentiviral vectors resulted in the inhibition of cell proliferation and the induction of cell death by apoptosis. In vivo, lentiviral administration of hIFN-β prevented PC tumor progression for up to 15 days following gene therapy, and induced tumor regression/stabilization in 50% of the mice treated. Again, hIFN-β expression resulted in cancer cell proliferation inhibition and apoptosis induction. We provide evidence that human immunodeficiency virus (HIV)-1-based lentiviral vectors are very efficient for gene transfer in PC-derived cells in vitro and in vivo. As a consequence, delivery of hIFN-β stopped PC tumor progression. Thus, our approach could be applied to the 85% of PC patients with a locally advanced disease.

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Acknowledgements

The authors thank the BSL-3 laboratory (plate-forme BiVIC IFR150) for vector production. In addition, the authors greatly thank Pr Jan Hoek for careful reading and editing of the paper. This work was supported by grants from INSERM, Région Midi-Pyrénées, and Cancéropôle Grand Sud-Ouest.

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Authors and Affiliations

  1. UMR 5241 CNRS-UPS, Centre Hospitalier Universitaire Rangueil, Toulouse, France

    E Ravet & L Casteilla

  2. I2MR département Cancer, Institut National de la Santé et de la Recherche Médicale U858, and Institut Louis Bugnard IFR150, Toulouse, France

    H Lulka, L Buscail & P Cordelier

  3. Clinical Investigation Center of Biothérapie (CIC-BT 511), Centre Hospitalier Universitaire Rangueil, Toulouse, France

    F Gross

  4. Department of Gastroenterology, Centre Hospitalier Universitaire Rangueil, Toulouse, France

    L Buscail

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  1. E Ravet
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Correspondence to P Cordelier.

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Ravet, E., Lulka, H., Gross, F. et al. Using lentiviral vectors for efficient pancreatic cancer gene therapy. Cancer Gene Ther 17, 315–324 (2010). https://doi.org/10.1038/cgt.2009.79

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