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Inhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice

PLoS ONE, ISSN: 1932-6203, Vol: 5, Issue: 9, Page: 1-9
2010
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Targeting Telomere Dynamics as an Effective Approach for the Development of Cancer Therapeutics

Introduction Telomere is a protective structure located at the end of the linear chromosome of eukaryotes, which is made up of tandem repetitive DNA sequences

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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. Methodology/Principal Finding: Immunocopetent 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 vg rAAV-hTERTC27 and 2.5×10 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. Conclusion: Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model. © 2010 Huo et al.

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http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77958583393&origin=inward; http://dx.doi.org/10.1371/journal.pone.0012705; http://www.ncbi.nlm.nih.gov/pubmed/20856939; https://dx.plos.org/10.1371/journal.pone.0012705.g004; http://dx.doi.org/10.1371/journal.pone.0012705.g004; https://dx.plos.org/10.1371/journal.pone.0012705.g001; http://dx.doi.org/10.1371/journal.pone.0012705.g001; https://dx.plos.org/10.1371/journal.pone.0012705.g005; http://dx.doi.org/10.1371/journal.pone.0012705.g005; https://dx.plos.org/10.1371/journal.pone.0012705.g003; http://dx.doi.org/10.1371/journal.pone.0012705.g003; https://dx.plos.org/10.1371/journal.pone.0012705; https://dx.plos.org/10.1371/journal.pone.0012705.g002; http://dx.doi.org/10.1371/journal.pone.0012705.g002; https://dx.doi.org/10.1371/journal.pone.0012705.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0012705.g004; https://dx.doi.org/10.1371/journal.pone.0012705; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012705; https://dx.doi.org/10.1371/journal.pone.0012705.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0012705.g003; https://dx.doi.org/10.1371/journal.pone.0012705.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0012705.g002; https://dx.doi.org/10.1371/journal.pone.0012705.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0012705.g005; https://dx.doi.org/10.1371/journal.pone.0012705.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0012705.g001; http://dx.plos.org/10.1371/journal.pone.0012705.g003; http://dx.plos.org/10.1371/journal.pone.0012705.g004; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012705; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012705&type=printable; http://dx.plos.org/10.1371/journal.pone.0012705.g001; http://dx.plos.org/10.1371/journal.pone.0012705.g005; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0012705; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0012705&type=printable; http://dx.plos.org/10.1371/journal.pone.0012705; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0012705; http://dx.plos.org/10.1371/journal.pone.0012705.g002

Longfei Huo; Hong Yao; Xicai Wang; Gee Wan Wong; Hsiang-fu Kung; Marie C. Lin; Jacques Zimmer

Public Library of Science (PLoS)

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