712. Treatment of Human and Rat Hepatocellular Carcinomas by Long Term Expression of rAAV-Mediated Transfer of Human TERTC27 Polypeptide

The re-activation of human telomerase reverse transcriptase (hTERT) plays a major role in the carcinogenesis of hepatocellular carcinoma (HCC). In Hong Kong, hTERT is activated in approximately 85% of the HCC patients. We have previously demonstrated that constitutive expression of a 27 kDa C-terminal fragment of human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorgenicity of hTERT positive human cervical cancer Hela cells (Huang et al., Cancer Res., 2002). In this study, the therapeutic effect of hTERTC27 was further tested in vivo in different models harboring either human or rat HCC. A recombinant adeno-associated virus (rAAV) plasmid encoding hTERTC27 was constructed and high-purity rAAV-hTERTC27 vectors were prepared. We first showed that intratumoral injection of rAAV-hTERTC27 is highly efficient in inhibiting the growth of human HCC, Hep3B cells, transplanted subcutaneously in nude mice. The expression of hTERTC27 in the tumor was confirmed by Western blotting analysis. Histological studies indicated that injection of rAAV-hTERTC27 produced profound apoptosis and necrosis in the TERT positive Hep3B cells.