Using lentiviral vectors for efficient pancreatic cancer gene therapy.
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.
Ravet
E
E
UMR 5241 CNRS-UPS, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Lulka
H
H
Gross
F
F
Casteilla
L
L
Buscail
L
L
Cordelier
P
P
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
D016899:Interferon-beta