Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein

H. Bian, P. Fournier, B.P.H. Peeters, V. Schirrmacher

    Research output: Contribution to journalArticleAcademicpeer-review

    18 Citations (Scopus)

    Abstract

    Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100% in liver, spleen, kidney, lung and thymus by the modified virus, while 98% of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues
    Original languageEnglish
    Pages (from-to)377-384
    JournalInternational Journal of Oncology
    Volume27
    Issue number2
    DOIs
    Publication statusPublished - 2005

    Fingerprint

    Newcastle disease virus
    Genes
    Neoplasms
    Proteins
    Transgenes
    Interleukin-2
    Viruses
    Gene Expression
    Viral Genes
    Interleukin-2 Receptors
    RNA Viruses
    Fluorescence Microscopy
    Thymus Gland
    Real-Time Polymerase Chain Reaction
    Lymphoma
    Spleen
    Kidney
    Lung
    Messenger RNA
    Injections

    Keywords

    • oncolytic virus
    • ovarian-cancer
    • phase-i
    • cells
    • replication
    • virotherapy
    • strains
    • vaccine
    • vector
    • pv701

    Cite this

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    title = "Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein",
    abstract = "Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100{\%} in liver, spleen, kidney, lung and thymus by the modified virus, while 98{\%} of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues",
    keywords = "oncolytic virus, ovarian-cancer, phase-i, cells, replication, virotherapy, strains, vaccine, vector, pv701",
    author = "H. Bian and P. Fournier and B.P.H. Peeters and V. Schirrmacher",
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    language = "English",
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    Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein. / Bian, H.; Fournier, P.; Peeters, B.P.H.; Schirrmacher, V.

    In: International Journal of Oncology, Vol. 27, No. 2, 2005, p. 377-384.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein

    AU - Bian, H.

    AU - Fournier, P.

    AU - Peeters, B.P.H.

    AU - Schirrmacher, V.

    PY - 2005

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    N2 - Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100% in liver, spleen, kidney, lung and thymus by the modified virus, while 98% of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues

    AB - Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100% in liver, spleen, kidney, lung and thymus by the modified virus, while 98% of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues

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