دورية أكاديمية
RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency.
| العنوان: | RNA interference-mediated silencing of Foxo3 in antigen-presenting cells as a strategy for the enhancement of DNA vaccine potency. |
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| المؤلفون: | Wang ST; Institute of Biomedical Sciences, College of Life Science, National Chung Hsing University, Taichung, Taiwan., Chang CC, Yen MC, Tu CF, Chu CL, Peng YT, Chen DY, Lan JL, Lin CC |
| المصدر: | Gene therapy [Gene Ther] 2011 Apr; Vol. 18 (4), pp. 372-83. Date of Electronic Publication: 2010 Nov 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5462 (Electronic) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Nature Publishing Group Original Publication: Houndmills, Basingstoke, Hampshire, UK : Macmillan Press Ltd., c1994- |
| مواضيع طبية MeSH: | Genes, erbB-2* , RNA Interference*, Antigen-Presenting Cells/*metabolism , Cancer Vaccines/*immunology , Forkhead Transcription Factors/*genetics , Vaccines, DNA/*immunology, Animals ; Antigen-Presenting Cells/immunology ; Biolistics ; Cell Line ; Chlorocebus aethiops ; Dendritic Cells/immunology ; Forkhead Box Protein O3 ; Genetic Vectors ; Humans ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; RNA, Small Interfering/pharmacology ; T-Lymphocytes/immunology ; Urinary Bladder Neoplasms/prevention & control |
| مستخلص: | The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8(+) T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8(+) T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors. |
| المشرفين على المادة: | 0 (Cancer Vaccines) 0 (Forkhead Box Protein O3) 0 (Forkhead Transcription Factors) 0 (FoxO3 protein, mouse) 0 (RNA, Small Interfering) 0 (Vaccines, DNA) |
| تواريخ الأحداث: | Date Created: 20101126 Date Completed: 20110708 Latest Revision: 20191210 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/gt.2010.146 |
| PMID: | 21107437 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1476-5462 |
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| DOI: | 10.1038/gt.2010.146 |