Gene therapy against ovarian cancers using hTERT promoter

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Telomerase activation has been observed in almost 90% of human cancers but not normal tissues of somatic origin. The recent research on the transcriptional regulation of hTERT promoter identified several factors, including c-Myc, SP1 and E2, which critically regulate promoter activity. The present study is based on the idea that the hTERT promoter can confer strong tumor-specific transgene expression, minimizing toxicity to normal cells, compared to the universal promoters. The following results were obtained from the present study.1) In vitro and in vivo administration of chimeric vectors in which hTERT promoter is linked to apoptosis-inducing genes, such as Caspase, FADD or Bax successfully induce apoptosis in cancer cells with damaging normal cell.2) The binary adenovirus system using two vectors, Ad/GT-BAX and Ad/hTERT-GV16 augmented the anti tumor-efficacy.3) The transfection of the vector designed to drive MCP-1 gene by hTERT promoter induced the expression of MCP-1 more extensively, compare to CMV-promoter. The multidisciplinary treatment of therapeutic vectors with MCP-1 gene and cisplatin suppressed significantly tumor growth in vivo.