File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleInhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 9, p. e12705 How to Cite?
AbstracthTERTC27 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. 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. Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.
Persistent Identifierhttp://hdl.handle.net/10722/145501
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Innovation and Technology FundITS/105/02
ITS/173/08
Funding Information:

The work was supported by grants from the Innovation and Technology Fund (ITS/105/02 and ITS/173/08 to M.C.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Grants

 

DC FieldValueLanguage
dc.contributor.authorHuo, Len_HK
dc.contributor.authorYao, Hen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, GWen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2012-02-27T03:09:18Z-
dc.date.available2012-02-27T03:09:18Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 9, p. e12705en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145501-
dc.description.abstracthTERTC27 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. 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. Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.en_HK
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.subject.meshCancer Vaccines-
dc.subject.meshCell Proliferation-
dc.subject.meshDown-Regulation-
dc.subject.meshMelanoma - drug therapy - immunology - physiopathology-
dc.subject.meshTelomerase - administration and dosage - genetics - immunology-
dc.titleInhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.en_HK
dc.typeArticleen_HK
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0012705-
dc.identifier.pmid20856939-
dc.identifier.pmcidPMC2938346-
dc.identifier.scopuseid_2-s2.0-77958583393en_HK
dc.identifier.hkuros182330-
dc.identifier.volume5en_HK
dc.identifier.issue9en_HK
dc.identifier.spagee12705en_HK
dc.identifier.epagee12705en_HK
dc.identifier.isiWOS:000281735700020-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectDevelopment of Novel Second Generation Broad-spectrum hTERTC27-based Therapeutic Tumor Vaccine-
dc.relation.projectCancer gene therapy using a novel anti-cancer polypeptide hTERTC27 delivered by a novel AAV and Adenovirus Cocktail vector system-
dc.identifier.scopusauthoridHuo, L=9275343500en_HK
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridWang, X=37008806000en_HK
dc.identifier.scopusauthoridWong, GW=36769467400en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats