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A Conditionally Replicating Adenovirus CNHK500 for the Treatment of Breast Cancer
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Abstract:
Objective: To evaluate the selectively oncolytic effect of conditionally replicating adenovirus CNHK500 in breast cancer. Methods: We used virus proliferation assay cell viability assay to evaluate the proliferation and cytolysis selectivity of CNHK500. And we used Western-blot to confirm the expression of adenovirus CNHK500 E1A and E1B in cancer and normal cells. Results: The CNHK500 virus proliferation ability in breast cancer cell lines is similar to that of wtAd5, better than that of ONYX-015 virus. However, CNHK500 virus replicate 1000-fold less than that of wtAd5 in normal fibroblast cell lines. CNHK500 can effectively kill breast cancer cell, while it shows attenuated cytolysis in normal fibroblast cells, with about 100-fold less than that of wtAd5. CNHK500 E1A is expressed in telomerase-positive breast cancer cells but not in telomerase-negative normal fibroblast cells. E1B protein can be detected under hypoxia condition but not in normoxia conditions. Intravenous injections of CNHK500, yielded significant tumor growth delay in the telomerase-positive breast cancer xenografts though the MCF-7 represent a very fast growing tumor cell line. Antitumor efficacy of replication-competent adenovirus CNHK500 in vivo was associated with increased dosage of CNHK500. Conclusions: The results prove that CNHK500 has highly proliferation selectivity and potent cytolysis effect on breast cancer.
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