Generation of a novel, cyclooxygenase-2–targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy - 08/11/12
Corresponding author. Tel.: +1-612-625-8608; fax: +1-612-624-9080Abstract |
Background |
Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated.
Methods |
Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens.
Results |
Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown.
Conclusions |
Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer–specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients.
Le texte complet de cet article est disponible en PDF.Keywords : Pancreatic cancer, Oncolytic virus, Adenovirus, Conditionally replicative adenovirus (CRAd), Gene therapy, Interferon-alfa, Adenoviral death protein (ADP), Cox2, Krumdiek tissue slicer
Plan
Vol 204 - N° 5
P. 741-750 - novembre 2012 Retour au numéro
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