Activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs) by human dendritic cells infected with an attenuated influenza A virus expressing a CTL epitope derived from the HER-2/neu proto-oncogene.


: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.


J Virol


Journal of virology


Efferson CL,Schickli J,Ko BK,Kawano K,Mouzi S,Palese P,García-Sastre A,Ioannides CG




Has Abstract


2003-07-01 00:00:00












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    authors: Sokol F,Stancek D,Koprowski H

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    authors: Reddy PS,Idamakanti N,Zakhartchouk AN,Baxi MK,Lee JB,Pyne C,Babiuk LA,Tikoo SK

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    authors: Meessen-Pinard M,Le Coupanec A,Desforges M,Talbot PJ

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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,评审


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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Caldwell RG,Brown RC,Longnecker R

    更新日期:2000-02-01 00:00:00

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    journal_title:Journal of virology

    pub_type: 杂志文章


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    更新日期:1992-01-01 00:00:00

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    pub_type: 杂志文章


    authors: Lynn H,Horsington J,Ter LK,Han S,Chew YL,Diefenbach RJ,Way M,Chaudhri G,Karupiah G,Newsome TP

    更新日期:2012-07-01 00:00:00