Histone deacetylase inhibitor AR-42 enhances E7-specific CD8(+) T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination
DC Field | Value | Language |
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dc.contributor.author | Lee, Sung Yong | - |
dc.contributor.author | Huang, Zhuomin | - |
dc.contributor.author | Kang, Tae Heung | - |
dc.contributor.author | Soong, Ruey-Shyang | - |
dc.contributor.author | Knoff, Jayne | - |
dc.contributor.author | Axenfeld, Ellen | - |
dc.contributor.author | Wang, Chenguang | - |
dc.contributor.author | Alvarez, Ronald D. | - |
dc.contributor.author | Chen, Ching-Shih | - |
dc.contributor.author | Hung, Chien-Fu | - |
dc.contributor.author | Wu, T. -C. | - |
dc.date.accessioned | 2021-09-05T20:52:16Z | - |
dc.date.available | 2021-09-05T20:52:16Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2013-10 | - |
dc.identifier.issn | 0946-2716 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/102072 | - |
dc.description.abstract | We have previously created a potent DNA vaccine encoding calreticulin linked to the human papillomavirus (HPV) oncogenic protein E7 (CRT/E7). While treatment with the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency with the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi has been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether co-administration of a novel HDACi, AR-42, with therapeutic HPV DNA vaccines could improve the activation of HPV antigen-specific CD8(+) T cells, resulting in potent therapeutic antitumor effects. To do so, HPV-16 E7-expressing murine TC-1 tumor-bearing mice were treated orally with AR-42 and/or CRT/E7 DNA vaccine via gene gun. Mice were monitored for E7-specific CD8(+) T cell immune responses and antitumor effects. TC-1 tumor-bearing mice treated with AR-42 and CRT/E7 DNA vaccine experienced longer survival, decreased tumor growth, and enhanced E7-specific immune response compared to mice treated with AR-42 or CRT/E7 DNA vaccine alone. Additionally, treatment of TC-1 cells with AR-42 increased the surface expression of MHC class I molecules and increased the susceptibility of tumor cells to the cytotoxicity of E7-specific T cells. This study indicates the ability of AR-42 to significantly enhance the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Both AR-42 and CRT/E7 DNA vaccines have been used in independent clinical trials; the current study serves as foundation for future clinical trials combining both treatments in cervical cancer therapy. Key message AR-42, a novel HDAC inhibitor, enhances potency of therapeutic HPV DNA vaccines AR-42 treatment leads to strong E7-specific CD8+ T cell immune responses AR-42 improves tumor-specific immunity and antitumor effects elicited by HPV DNA vaccine AR-42 is more potent than clinically available HDACi in combination with HPV DNA vaccine. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER HEIDELBERG | - |
dc.subject | MHC CLASS-I | - |
dc.subject | DENDRITIC CELLS | - |
dc.subject | CANCER | - |
dc.subject | TUMOR | - |
dc.subject | CALRETICULIN | - |
dc.subject | GENE | - |
dc.subject | VORINOSTAT | - |
dc.subject | EXPRESSION | - |
dc.subject | EFFICACY | - |
dc.subject | PROTEIN | - |
dc.title | Histone deacetylase inhibitor AR-42 enhances E7-specific CD8(+) T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Sung Yong | - |
dc.identifier.doi | 10.1007/s00109-013-1054-9 | - |
dc.identifier.scopusid | 2-s2.0-84885329272 | - |
dc.identifier.wosid | 000324673300010 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MOLECULAR MEDICINE-JMM, v.91, no.10, pp.1221 - 1231 | - |
dc.relation.isPartOf | JOURNAL OF MOLECULAR MEDICINE-JMM | - |
dc.citation.title | JOURNAL OF MOLECULAR MEDICINE-JMM | - |
dc.citation.volume | 91 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1221 | - |
dc.citation.endPage | 1231 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | MHC CLASS-I | - |
dc.subject.keywordPlus | DENDRITIC CELLS | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | TUMOR | - |
dc.subject.keywordPlus | CALRETICULIN | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | VORINOSTAT | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordAuthor | Cancer vaccine | - |
dc.subject.keywordAuthor | Human papillomavirus | - |
dc.subject.keywordAuthor | Cervical cancer | - |
dc.subject.keywordAuthor | Histone deacetylase inhibitor | - |
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