Inhibition of Melanoma Development by Single Dose Administration of hTERTC27 Viral Cocktail in C57BL/6 Mice

Abstract

hTERTC27, a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase, has been previously demonstrated to reduce the tumorigenicity of HeLa cells. We report here that a rAAV-/rAdvviral cocktail expressing hTERTC27 peptide can induce growth inhibition of transplanted melanoma tumors in immunocompetent C57BL/6 mice. Melanoma B16 tumor growth was significantly inhibited by subcutaneous administration with a single dose of 1.5 ×1011 vg rAAV-hTERTC27 and 2.5×109 pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27). The population of NK cells and the levels of cytokines, including IL-2, IFN-g and GM-CSF, in serum were markedly increased after administration of the hTERTC27 rAAW-/rAdv-viral cocktail. The specific cytotoxicity of NK cells in mice treated with rAAV-/rAdv-hTERTC27 viral cocktail was also significantly higher than that observed in control mice treated with rAAV-/rAdv-EGFP viral cocktail and PBS. These results, demonstrated for the first time that the subcutaneous administration of rAAV-/rAdv-hTERTC27 viral cocktail could induce strong innate immunity against melanoma. Furthermore, single dose injection of rAAV-rAdv-hTERTC27 exhibited no detectable toxicity. This indicates that rAAV-rAdv hTERTC27 might be a suitable palliative and system therapy in patients with advanced melanoma.