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Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy

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Abstract

Therapeutic cancer vaccines need to stimulate a refractory immune system to make an effective anti-tumour response. We have explored the use of lentiviral vectors to deliver tumour antigen genes to dendritic cells (DC) as a possible mechanism of immune stimulation. Direct injection of a lentiviral vector encoding the melanoma antigen NY-ESO-1 in HLA-A2 transgenic mice primed NY-ESO-1-specific CD8+ cells that could be expanded by boosting with an NY-ESO-1 vaccinia virus. The expanded cells could kill NY-ESO-1157–165 peptide-pulsed targets in vivo. In order to examine the priming step directly, we constructed another lentiviral vector expressing the melanoma antigen Melan-A (MART-1). Here we show that Melan-A protein is also efficiently expressed after transduction of human DC cultured from peripheral blood mononuclear cells. When these transduced DC are co-cultured with autologous naïve T cells, they cause the expansion of cells that recognise the HLA-A2 restricted Melan-A27–35 epitope. The expanded cells are functional in that they release IFN-γ upon antigen stimulation. Melan-A lentiviral vector transduced DC caused a similar level of naïve T-cell expansion to Melan-A27–35 peptide-pulsed DC in four experiments using different HLA-A2 positive donors. These data suggest that a vaccine based either on DC transduced with a lentiviral vector ex vivo, or on direct lentiviral vector injection, should be assessed in a phase I clinical trial.

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Authors and Affiliations

  1. Infection and Immunity, University College London, Windeyer Building, 46 Cleveland St, W1T 4JF, London, UK

    Luciene Lopes, Kate Fletcher, Yasuhiro Ikeda & Mary Collins

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  1. Luciene Lopes
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  2. Kate Fletcher
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  3. Yasuhiro Ikeda
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  4. Mary Collins
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Corresponding author

Correspondence to Mary Collins.

Additional information

This article is a symposium paper from the “Robert Baldwin Symposium: 50 years of Cancer Immunotherapy”, held in Nottingham, Great Britain, on 30th June 2005.

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Lopes, L., Fletcher, K., Ikeda, Y. et al. Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy. Cancer Immunol Immunother 55, 1011–1016 (2006). https://doi.org/10.1007/s00262-005-0095-5

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  • DOI: https://doi.org/10.1007/s00262-005-0095-5

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