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Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy

Gene Therapy volume 14, pages 1639–1649 (2007)Cite this article

Abstract

This is the first report describing recombinant (rec) Newcastle disease virus (NDV) as vector for gene therapy of cancer. The gene encoding granulocyte/macrophage colony-stimulating factor (GM-CSF) was inserted as an additional transcription unit at two different positions into the NDV genome. The rec virus with the strongest production of the gene product (rec(GM-CSF)) was selected for our study. The insertion of the new foreign gene did neither affect the main features of NDV replication nor its tumor selectivity. The gene product was biologically active and stable. Tumor vaccine cells infected by rec(GM-CSF) stimulated human peripheral blood mononuclear cells (PBMC) to exert antitumor bystander effects in vitro in a tumor neutralization assay. These effects were significantly increased when compared to vaccine infected by rec(−) virus. Furthermore, rec(GM-CSF) led to a much higher interferon-α (IFN-α) production than rec(−) when added as virus or as virus-modified vaccine to PBMC. Two distinct cell types, monocytes and plasmacytoid dendritic cells were shown to contribute to the augmented IFN-α response of PBMC. In conclusion, the already inherent anti-neoplastic and immunostimulatory properties of NDV could be further augmented by the introduction of a therapeutic gene whose product initiates a broad cascade of immunological effects in the microenvironment of the vaccine.

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Author information

Authors and Affiliations

  1. Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany

    M Janke, A Arnold, P Fournier & V Schirrmacher

  2. Division of Virology, Central Institute for Animal Disease Control Lelystad (CIDC-Lelystad), Lelystad, The Netherlands

    B Peeters

  3. Division of Infectious Diseases, Animal Sciences Group, Wageningen University and Research Centre, Lelystad, The Netherlands

    O de Leeuw & R Moorman

  4. Division of Clinical Pharmacology, University Hospital, University of Bonn, Sigmund-Freud-Street 25, Bonn, Germany

    M Janke

Authors
  1. M Janke
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  2. B Peeters
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  3. O de Leeuw
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  4. R Moorman
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  5. A Arnold
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  6. P Fournier
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  7. V Schirrmacher
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Correspondence to V Schirrmacher.

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Janke, M., Peeters, B., de Leeuw, O. et al. Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther 14, 1639–1649 (2007). https://doi.org/10.1038/sj.gt.3303026

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