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Using lentiviral vectors for efficient pancreatic cancer gene therapy.

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-beta) gene. Expression of hIFN-beta 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-beta 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-beta 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-beta 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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https://www.hal.inserm.fr/inserm-00480870
Contributor : Marie Francoise Simon <>
Submitted on : Wednesday, May 5, 2010 - 11:23:45 AM
Last modification on : Friday, January 10, 2020 - 9:09:49 PM

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Emmanuel Ravet, Hubert Lulka, F. Gross, Louis Casteilla, Louis Buscail, et al.. Using lentiviral vectors for efficient pancreatic cancer gene therapy.. Cancer Gene Therapy, Nature Publishing Group, 2010, 17 (5), pp.315-24. ⟨10.1038/cgt.2009.79⟩. ⟨inserm-00480870⟩

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