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Induction of effective therapeutic antitumor immunity by direct in vivo administration of lentiviral vectors

Gene Therapy volume 13, pages 630–640 (2006)Cite this article

Abstract

Ex vivo lentivirally transduced dendritic cells (DC) have been described to induce CD8+ and CD4+ T-cell responses against various tumor-associated antigens (TAAs) in vitro and in vivo. We report here that direct administration of ovalbumin (OVA) encoding lentiviral vectors caused in vivo transduction of cells that were found in draining lymph nodes (LNs) and induced potent anti-OVA cytotoxic T cells similar to those elicited by ex vivo transduced DC. The cytotoxic T-lymphocyte (CTL) response following direct injection of lentiviral vectors was highly effective in eliminating target cells in vivo up to 30 days after immunization and was efficiently recalled after a boost immunization. Injection of lentiviral vectors furthermore activated OVA-specific CD4+ T cells and this CD4 help was shown to be necessary for an adequate primary and memory CTL response. When tested in therapeutic tumor experiments with OVA+ melanoma cells, direct administration of lentiviral vectors slowed down tumor growth to a comparable extent with the highest dose of ex vivo transduced DC. Taken together, these data indicate that direct in vivo administration of lentiviral vectors encoding TAAs has strong potential for anticancer vaccination.

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Abbreviations

DC:

dendritic cells

CM:

complete medium

TU:

transducing units

LN:

lymph node

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Acknowledgements

We thank Elsy Vaeremans and Margareth Verbuyst for DNA preparations, Julie De Meester for help with the tumor experiments and Delphine Baup for the supply of the OT-II mice and the GK1.5 antibody. MD was supported by a grant from the Fund for Scientific Research Flanders (FWO-Vlaanderen). This work was further supported by grants to K T from the FWO-Vlaanderen, the IWT, the Ministry of Science (IUAP/PAI), the Fortis Bank and the ‘Belgische Federatie voor Kankerbestrijding’.

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  1. Department of Physiology-Immunology, Laboratory of Molecular and Cellular Therapy, Medical School of the Vrije Universiteit Brussel (VUB), Brussels, Belgium

    M Dullaers, S Van Meirvenne, C Heirman, L Straetman, A Bonehill, J L Aerts, K Thielemans & K Breckpot

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  1. M Dullaers
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Correspondence to K Thielemans.

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Dullaers, M., Meirvenne, S., Heirman, C. et al. Induction of effective therapeutic antitumor immunity by direct in vivo administration of lentiviral vectors. Gene Ther 13, 630–640 (2006). https://doi.org/10.1038/sj.gt.3302697

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