Lentivirally transduced dendritic cells as a tool for cancer immunotherapy.

Breckpot K, Dullaers M, Bonehill A, van Meirvenne S, Heirman C, de Greef C, van der Bruggen P, Thielemans K.
J Gene Med. 2003 Aug;5(8):654-67

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 huIi80MAGE-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 huIi80MAGE-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 2003 John Wiley & Sons, Ltd.

URL: http://www3.interscience.wiley.com/journal/104527933/abstract

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/12898635

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