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Selective gene transfer in vitro to tumor cells via recombinant Newcastle disease virus

Cancer Gene Therapy volume 12, pages 295–303 (2005)Cite this article

Abstract

We developed a novel strategy to target recombinant Newcastle disease virus (NDV) to tumor cells for gene therapy. Modifying the virus with a bispecific fusion protein allowed virus receptor-independent tumor cell binding and gene transfer. The targeting molecule αHN-IL-2 contains an scFv antibody cloned from a neutralizing hemagglutinin-neuraminidase (HN)-specific hybridoma linked to the human cytokine IL-2. A recombinant NDV expressing the enhanced green fluorescent protein (NDFL-EGFP) was applied to show the expression of foreign genes in virus-infected tumor cells. At 24 hours after infection with the modified virus (NDFL-EGFP/αHN-IL-2), FACS analysis and fluorescence microscopy revealed neutralization of natural infection in IL-2 receptor-negative Jurkat leukemia cells, but targeted expression of EGFP in IL-2 receptor-positive human leukemia-derived MT-2 cells. The targeted gene delivery of NDFL-EGFP/αHN-IL-2 in MT-2 cells was blocked by the target ligand human IL-2. Selective virus entry to IL-2 receptor bearing tumor cells was also observed in a mixture of Jurkat and MT-2 cell lines. These results demonstrate that a recombinant NDV carrying a foreign gene can be successfully targeted to a specific tumor through a bispecific protein, which thereby increases the selectivity of gene transfer.

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Authors and Affiliations

  1. Division of Cellular Immunology, German Cancer Research Center, D010, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Huijie Bian, Philippe Fournier & Volker Schirrmacher

  2. Animal Sciences Group, Wageningen UR, Division of Infectious Diseases, PO Box 65, 8200 AB, Lelystad, The Netherlands

    Rob Moormann & Ben Peeters

  3. Cell Engineering Research Center, Fourth Military Medical University, Xi'an, 710032, China

    Huijie Bian

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  1. Huijie Bian
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  2. Philippe Fournier
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  5. Volker Schirrmacher
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Correspondence to Volker Schirrmacher.

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Bian, H., Fournier, P., Moormann, R. et al. Selective gene transfer in vitro to tumor cells via recombinant Newcastle disease virus. Cancer Gene Ther 12, 295–303 (2005). https://doi.org/10.1038/sj.cgt.7700774

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