In Vivo Tumor Suppression by Adenovirus-Mediated Interferon alpha2b Gene Delivery

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Abstract
A replication-deficient adenovirus encoding human interferon alpha 2b, driven by the human cytomegalovirus (CMV) promoter, was constructed and characterized. This construct was used to infect human cells derived from different types of cancer. The production of protein and its secretion into the culture medium were tested by Western blotting and immunoassay. Inhibition of cell proliferation and antiviral activity, two of the most important biological activities of interferon, were observed with this construct. PC-3 cells, derived from hu- man prostatic cancer, or Hep3B cells, derived from human hepatocellular carcinoma, were injected subcuta- neously to generate and establish in vivo tumors in athymic nude mice. Intratumoral injection with the re- combinant adenovirus expressing interferon alpha 2b resulted in complete regression of tumor growth. Our results demonstrate that interferon gene delivery using recombinant adenoviral vectors may be a useful approach to treat a variety of cancers.