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Selective Replication in vitro and mIFN-γ Expression of a Tumor-Specific Replicative Virus CNHK200-mIFN-γ
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Abstract:
Objectives: To construct the replication-competent adenovirus CNHK200--mIFN-γ and the replication-deficient adenovirus AdEasy-mIFN-γ, and to compare their expression of mIFN-γ and the replicative activities of CNHK200-mIFN-γ，ONYX-015 and wide-type adenovirus (Ad5) in normal and cancer cells. Their antitumor activities were also observed.Methods:The replicative activities of viruses in cells were measured by viral replication assay; The replication of CNHK200-mIFN-γ in Hep3B cells was observed under the electron microscopy; The expression of mIFN-γ in cancer cells was detected by ELISA. CPE assay was used to detect viral antitumor activity.Results: Both CNHK200-mIFN-γ and ONYX-015 replicated only in cancer cells, and CNHK200-mIFN-γ replicated more potential than ONYX-015; The infection of CNHK200-mIFN-γ led to an obvious expression of mIFN-γ, whereas the expression of mIFN-γ mediated by AdEasy-mIFN-γ could not be detected at all. CNHK200-mIFN-γ and ONYX-015 could kill cancer cells but spare normal cells. Conclusions: The insertion of mIFN-γ causes no alterations on the tumor-specific replication of the original virus. CNHK200-mIFN-γ can selectively replicate and effectively express mIFN-γ in tumor cells, and specifically kill cancer cells, suggesting a splendid future as a new anticancer agent.
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