期刊
VACCINE
卷 25, 期 45, 页码 7824-7831出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2007.08.036
关键词
human papillomavirus-16 (HPV-16); E6 single chain trimer (SCT); dendritic cells; cancer immunotherapy; BclxL; DNA vaccines; tumor treatment
资金
- NCI NIH HHS [P50 CA098252-02, R01 CA072631-04, P50 CA098252-03, P50 CA098252, R01 CA114425-02, P50 CA098252-02S1, R01 CA072631-03, R01 CA114425-03, P50 CA098252-01, R01 CA114425-01, 1 RO1 CA114425-01, R01 CA072631-05, R01 CA114425] Funding Source: Medline
Intradermal vaccination via gene gun efficiently delivers DNA vaccines into dendritic cells (DCs) of the skin, resulting in the activation and priming of anti,,en-specific T cells in vivo. We have previously demonstrated that intradermal delivery of DNA vaccines encoding single-chain trimer (SCT) composed of the most immunogenic epitope of human papillomavirus type 16 (HPV-16) E6 protein (aa49-57), beta 2-microglobulin, and MHC class I heavy chain (SCT-E6) can bypass antigen processing and lead to stable cell-surface presentation of E6 peptides. We also showed that co-administration of DNA vaccines with DNA encoding anti-apoptotic proteins can prolong the survival of DNA-transduced DCs. resulting in significant enhancement of antigen-specific CD8(+) T cell immune responses. In the current study, we hypothesized that combining the SCT strategy and antiapoptotic strategy may further enhance DNA vaccine potency by augmenting antigen-specific CD8(+) T cell immune responses and antitumor effects in vaccinated mice. Here, we show that C57BL/6 mice vaccinated with SCT-E6 DNA combined with antiapoptotic protein Bcl-xL DNA generated enhanced E6-specific CD8(+) T cell immune responses compared to mice vaccinated with SCT-E6 DNA and a non-functional mutant Bcl-xL (mtBcl-xL) DNA. Furthermore, we show that mice treated with SCT-E6 and Bcl-xL DNA generated enhanced anti-tumor effects against E6-expressing turner cells (TC-1/Luciferase) compared to mice treated with SCT-E6 and mtBcl-xL DNA. (c) 2007 Elsevier Ltd. All rights reserved.
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