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    Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.

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    Authors
    Brown, Michael D
    Zhang, Y
    Dermime, Said
    De Wynter, Erika A
    Hart, Claire A
    Kitchener, Henry C
    Stern, Peter L
    Skinner, M A
    Stacey, S N
    Affiliation
    Cancer Research Campaign Laboratories, Paterson Institute of Cancer Research, Christie Hospital, Manchester, UK.
    Issue Date
    2000-10
    
    Metadata
    Show full item record
    Abstract
    The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.
    Citation
    Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity. 2000, 7 (19):1680-9 Gene Ther.
    Journal
    Gene Therapy
    URI
    http://hdl.handle.net/10541/86669
    DOI
    10.1038/sj.gt.3301288
    PubMed ID
    11083477
    Type
    Article
    Language
    en
    ISSN
    0969-7128
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.gt.3301288
    Scopus Count
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    All Paterson Institute for Cancer Research

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