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Epstein–Barr virus vector-mediated gene transfer into human B cells: potential for antitumor vaccination

Gene Therapy volume 13, pages 150–162 (2006)Cite this article

Abstract

The efficient gene transfer of immunostimulatory cytokines into autologous tumor cells or the transfer of tumor-associated antigens into professional antigen-presenting cells is a prerequisite for many immunotherapeutic approaches. In particular with B cells, the efficiency of gene uptake is one of the limiting factors in cell-based vaccine strategies, since normal and malignant human B cells are commonly refractory to transducing gene vectors. Due to its natural tropism for human B cells, Epstein–Barr virus (EBV), a human herpes virus, might be an option, which we wanted to explore. EBV efficiently infects human B cells and establishes a latent infection, while the viral genome is maintained extrachromosomally. Although these characteristics are attractive, EBV is an oncogenic virus. Here, we present a novel EBV-derived vector, which lacks three EBV genes including two viral oncogenes and an essential lytic gene, and encodes granulocyte-macrophage colony-stimulating factor (GM-CSF) as a cytokine of therapeutic interest. We could show that EBV vectors efficiently transduce different B-cell lines, primary resting B cells, and tumor cells of B-cell lineage. Vector-derived GM-CSF was expressed in sufficient amounts to support the maturation of dendritic cells and their presentation of model antigens to cognate T-cell clones in autologous settings and an allogeneic, HLA-matched assay. We conclude that the EBV vector system might offer an option for ex vivo manipulation of B cells and gene therapy of B-cell lymphomas.

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Acknowledgements

This work was supported by the Sanderstiftung to RM and WH, by Grants Ha1354/3 and SFB455 of the Deutsche Forschungsgemeinschaft, and by Public Health Service Grant CA70723 to WH.

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Authors and Affiliations

  1. Department of Gene Vectors, GSF-National Research Center for Environment and Health, Munich, Germany

    E Hellebrand, G Reisbach & W Hammerschmidt

  2. Institute of Molecular Immunology, Munich, Germany

    E Hellebrand & R Mocikat

  3. Institute of Clinical Molecular Biology and Tumor Genetics, Munich, Germany

    J Mautner & F Nimmerjahn

  4. Clinic I of Internal Medicine, University of Cologne, Cologne, Germany

    M Hallek

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  1. E Hellebrand
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  2. J Mautner
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Correspondence to W Hammerschmidt.

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Hellebrand, E., Mautner, J., Reisbach, G. et al. Epstein–Barr virus vector-mediated gene transfer into human B cells: potential for antitumor vaccination. Gene Ther 13, 150–162 (2006). https://doi.org/10.1038/sj.gt.3302602

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