714. Adenoassociate Virus Mediated Long Term Expression of Human TERTC27 Polypeptide Inhibited Glioblastoma Carcinogenesis by Multiple Mechanisms

We have previously reported that ectopic expression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and reduces tumorgenicity of human cervical cancer Hela cells. Here we further demonstrated the therapeutic effect and molecular mechanisms of hTERTC27 mediated cancer gene therapy in vivo in established human glioblastoma U87 tumor. We showed that intra-tumoral injection of rAAV-hTERTC27 is highly effective in treating established tumors in vivo in subcutaneously transplanted glioblastoma tumors. Histological analysis showed that hTERTC27 caused profound apoptosis and necrosis in the TERT positive U87 tumors. To study the molecular mechanism of AAV-hTERTC27-mediated anti-tumor effects, we analyzed the global gene expression profile of the AAV-hTERTC27-injected tumor tissues as compared to that of the control AAV-EGFP-injected tumor tissues using cDNA microarray and proteomic approaches. Our results suggest that hTERTC27 exerts its effect by complex mechanisms which involve pathways in apoptosis, cell cycle, and more importantly marked host immune responses.