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.
|Original language||English (US)|
|Number of pages||10|
|Journal||American journal of surgery|
|State||Published - Nov 2012|
Bibliographical noteFunding Information:
Supported in part by the National Cancer Institute ( T32CA132715 to S.V., L.A.), by the National Cancer Institute ( P50CA101955 to J.D., S.V., M.Y.), by the National Cancer Institute ( R01CA094084 to M.Y., S.V., J.D.), and by the National Institute for Minority Health Disparities ( NIMHD/NIH-1P60MD003422 to S.V., J.H.).
- Adenoviral death protein (ADP)
- Conditionally replicative adenovirus (CRAd)
- Gene therapy
- Krumdiek tissue slicer
- Oncolytic virus
- Pancreatic cancer