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Lentivirally transduced dendritic cells as a tool for cancer immunotherapy

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Breckpot, K Dullaers, M Bonehill, A Van Meirvenne, S Heirman, C. van der Bruggen, Pierre [UCL] Thielemans, K.

Background Dendritic cells (DC) are the professional antigen-presenting cells of the immune system, fully equipped to prime naive T cells and thus essential components for cancer immunotherapy. Methods We tested the influence of several elements (cPPT, trip, WPRE, SIN) on the transduction efficiency of human DC. Human and murine DC were transduced with tNGFR-encoding lentiviruses to assess the effect of transduction on phenotype and function. Human DC were transduced with lentiviruses encoding huli80MAGE-A3 and murine DC with huIi80tOVA to test antigen presentation. Results A self-inactivating (SIN) lentiviral vector containing the trip element was most efficient in transducing human DC. The transduction of DC with trip/SIN tNGFR encoding lentiviral vectors at MOI 15 resulted in stable gene expression in up to 94.6% (murine) and 88.2% (human) of the mature DC, without perturbing viability, phenotype and function. Human huli80MAGE-A3-transduced DC were able to stimulate MAGE-A3-specific CD4(+) and CD8(+) T cell clones and could prime both MAGE-A3-specific CD4+ and CD8+ T cells in vitro. Murine huIi80tOVA-transduced DC were able to present OVA peptides in the context of MHC class I and class II in vitro and induced a strong OVA-specific cytotoxic T lymphocyte response in vivo, that was protective against subsequent challenge with OVA-expressing tumor cells. Conclusions We show that, using lentiviral vectors, efficient gene transfer in human and murine DC can be obtained and that these DC can elicit antigen-specific immune responses in vitro and in vivo. The composition of the transfer vector has a major impact on the transduction efficiency. Copyright (C) 2003 John Wiley Sons, Ltd.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2003
Language Anglais
Journal information "Journal of Gene Medicine" - Vol. 5, no. 8, p. 654-667 (2003)
Peer reviewed yes
Publisher John Wiley & Sons Ltd (Chichester)
issn 1099-498X
e-issn 1521-2254
Publication status Publié
Affiliation UCL
Keywords dendritic cell ; lentivirus ; immunotherapy ; T helper cell ; cytotoxic T cell
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Bibliographic reference Breckpot, K ; Dullaers, M ; Bonehill, A ; Van Meirvenne, S ; Heirman, C. ; et. al. Lentivirally transduced dendritic cells as a tool for cancer immunotherapy. In: Journal of Gene Medicine, Vol. 5, no. 8, p. 654-667 (2003)
Permanent URL http://hdl.handle.net/2078.1/40824