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

H. Bian, P. Fournier, R.J.M. Moormann, B.P.H. Peeters, V. Schirrmacher

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    23 Citations (Scopus)


    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 HN-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/HN-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/HN-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.
    Original languageEnglish
    Pages (from-to)295-303
    JournalCancer Gene Therapy
    Publication statusPublished - 2005


    • single-chain antibody
    • foreign gene
    • fusion protein
    • rna viruses
    • cloned cdna
    • expression
    • adenovirus
    • carcinoma
    • antigen
    • vaccine


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