Abstract:
:The development of cancer vaccines requires approaches to induce expansion and functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL) effectors which posses cytolytic capability and produce cytokines. Efficient induction of such cells is hindered by the poor immunogenicity of tumor antigens and by the poor transduction efficiency of dendritic cells (DCs) with current nonreplicating vectors. We have investigated the use of influenza A virus, a potent viral inducer of CTLs, as a vector expressing the immunodominant HER-2 CTL epitope KIF (E75). For this purpose, an attenuated influenza A/PR8/34 virus with a truncated nonstructural (NS1) gene was generated containing the E75 epitope in its neuraminidase protein (KIF-NS virus). Stimulation of peripheral blood mononuclear cells from healthy donors and of tumor-associated lymphocytes from ovarian and breast cancer patients with DCs infected with KIF-NS virus (KIF-NS DC) induced CTLs that specifically recognized the peptide KIF and HER-2-expressing tumors in cytotoxicity assays and secreted gamma interferon (IFN-gamma) and interleukin-2 at recall with peptide. Priming with KIF-NS DCs increased the number of E75(+) CD45RO(+) cells by more than 10-fold compared to nonstimulated cells. In addition, KIF-NS virus induced high levels of IFN-alpha in DCs. This is the first report demonstrating induction of human epitope-specific CTLs against a tumor-associated antigen with a live attenuated recombinant influenza virus vector. Such vectors may provide a novel approach for tumor antigen delivery, lymphocyte activation, and differentiation in human cancer vaccine development.
journal_name
J Viroljournal_title
Journal of virologyauthors
Efferson CL,Schickli J,Ko BK,Kawano K,Mouzi S,Palese P,García-Sastre A,Ioannides CGdoi
10.1128/jvi.77.13.7411-7424.2003subject
Has Abstractpub_date
2003-07-01 00:00:00pages
7411-24issue
13eissn
0022-538Xissn
1098-5514journal_volume
77pub_type
杂志文章abstract::Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We observed striking CD8+ T-ce...
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doi:10.1128/JVI.73.10.8196-8200.1999
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6923-6929.1999
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01832-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02039-07
更新日期:2008-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1307-1309.1974
更新日期:1974-11-01 00:00:00
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.7.3257-3266.2002
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2001-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00552-14
更新日期:2014-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.57.1.379-384.1986
更新日期:1986-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.7.3624-3633.2006
更新日期:2006-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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