Establishment of novel cancer therapy using telomerase-specific replication competent adenovirus

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We previously cloned the promoter of human reverse transcriptase (hTERT) gene, a catalytic subunit of human telomerase, which was found to be active only in cancer cells with telomerase activity, while it was silent in most normal cells without telomerase activity. We have planned to insert this promoter into the upstream of the El gene of Adenovirus type 5 genome so that adenovirus El gene is efficiently expressed only in cancer cells. Eventually, this chimera virus can replicate only in cancer cells with high levels of expression of El gene, which is required for viral replication. We named this virus TRAD: telomerase-specific replication adenovirus. In the present project, we examined the in vitro and in vivo efficacy of TARD directly injected into primary site of tumors. We found that TARD was effective to reduce tumor burden without exhibiting any severe adverse effect, such as myelosurpression or liver dysfunction caused by viral toxicity Therefore, we propose the clinical use of this virus.