title: 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.
authors.affiliation: UMR 5241 CNRS-UPS, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
authors.forename: E
authors.initials: E
authors.lastname: Ravet
authors.forename: H
authors.initials: H
authors.lastname: Lulka
authors.forename: F
authors.initials: F
authors.lastname: Gross
authors.forename: L
authors.initials: L
authors.lastname: Casteilla
authors.forename: L
authors.initials: L
authors.lastname: Buscail
authors.forename: P
authors.initials: P
authors.lastname: Cordelier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000502:physiology; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000628:therapy*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D016899:Interferon-beta