Inhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.
BACKGROUND
hTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress growth of xenografted glioblastoma in nude mice. Although ectopic expression of hTERTC27 upregulated genes that are involved in apoptosis, cell cycle, and immune response, the mechanism for hTERTC27-induced tumor suppression has not been completely elucidated. Since hTERT was identified as a universal tumor-associated antigen, we hypothesize that hTERTC27 inhibits tumor growth in vivo through activation of anti-tumor immune response.


RESULTS
Immunocompetent C57BL/6 mice were used for mouse B16 melanoma model. Mice bearing B16 melanoma were administered rAAV-/rAdv viral cocktail expressing hTERTC27, and tumor growth was monitored after viral cocktail treatment. Blood and splenocytes were used to determine the level of cytokines and the activity of immune cells, respectively. B16 tumor growth was significantly inhibited by subcutaneous administration of a single dose of 1.5×10(11) vg rAAV-hTERTC27 and 2.5×10(9) pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27). The population and cytotoxicity of NK cells in the mice were significantly augmented by rAAV-/rAdv-hTERTC27 treatment, and selective depletion of the NK cell population in mice by intraperitoneal injection of anti-GM1 antibody abrogated the growth suppression of melanoma induced by rAAV-/rAdv-hTERTC27 administration.


CONCLUSIONS
Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.
Huo
Longfei
L
Open Laboratory of Chemical Biology of the Institute of Molecular Technology, Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
Yao
Hong
H
Wang
Xicai
X
Wong
Gee Wan
GW
Kung
Hsiang-fu
HF
Lin
Marie C
MC
D000279:Administration, Cutaneous; D000818:Animals; D019496:Cancer Vaccines; D049109:Cell Proliferation; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019098:Telomerase / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology
D019496:Cancer Vaccines; C509186:TERT protein, human; D019098:Telomerase