Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein

Bian, Huijie; Fournier, Philippe; Moormann, R.J.M.; Peeters, Ben; Schirrmacher, Volker

doi:10.3892/ijo.26.2.431

Cited by 16 publications

(21 citation statements)

References 42 publications

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“…We demonstrated previously that retargeted tumor cell infection depends on specific recognition of IL-2 receptor by virus bound ·HN-IL-2 and on the viral F protein (18). We also showed that NDV replication is tumor selective (41) and associated with defects of tumor cells in antiviral defence (42).…”

Section: Discussionmentioning

confidence: 71%

“…This protein did compete with anti-HN mAb but not with anti-F mAb (18). Upon binding to NDV, this adapter molecule increased the stability of the virus upon culture at 37˚C (18).…”

Section: Antibodies and Bispecific Fusion Proteinmentioning

confidence: 99%

“…Previously, we showed that a lentogenic recombinant NDV (NDFL-EGFP) carrying the reporter gene coding for INTERNATIONAL JOURNAL OF ONCOLOGY 29: 1359-1369 In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein (17) and ex vivo (18,19) to receptor-defined tumor cells by the addition of an adapter molecule. This protein (·HN-IL-2) contains an scFv antibody cloned from a neutralizing HN-specific hybridoma linked to human interleukin-2 (IL-2).…”

Section: Introductionmentioning

confidence: 99%

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In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

Bian

Wilden²,

Fournier³

et al. 2006

Int J Oncol

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Abstract. The aim of the study was: i) to specifically target tumor tissue by Newcastle disease virus (NDV) with oncolytic properties, ii) to improve the delivery system for systemic application of NDV via a bispecific adapter protein and iii) to investigate anti-tumor activity and side-effects. We selected two oncolytic virus strains, one native and the other recombinant, which showed multicyclic replication patterns in tumor cells. In order to reduce normal cell binding, they were modified by preincubation with a recombinant bispecific protein which blocks the viral native cell binding site and introduces a new binding site for a tumor-associated target (in this study, the interleukin-2-receptor, IL-2R). After intravenous transfer to mice, uptake of modified NDV in liver, spleen, kidney and lung was greatly reduced in comparison to unmodified NDV as determined by RRT-PCR of viral M gene copies. In IL-2R + tumor bearing mice, the same assay revealed a high replication efficiency of the modified virus in the tumor tissue. Tumor therapy experiments showed that the side-effects induced by systemic application were greatly reduced by the adapter protein and that the anti-tumor effects were mostly undiminished. The demonstration of significant systemic anti-tumor activity of this viral vector suggests potential for augmentation by inclusion of one or more therapeutic genes.

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Section: Discussionmentioning

confidence: 71%

“…This protein did compete with anti-HN mAb but not with anti-F mAb (18). Upon binding to NDV, this adapter molecule increased the stability of the virus upon culture at 37˚C (18).…”

Section: Antibodies and Bispecific Fusion Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

Bian

Wilden²,

Fournier³

et al. 2006

Int J Oncol

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“…Our previous in vitro studies showed that lentogenic recombinant NDV with monocyclic replication properties can be retargeted to the IL-2R + human leukemia-like cell line, MT-2, by ·HN-IL-2, while the native tropism via the interaction between HN proteins and sialic-acid containing receptors was abolished (16). Furthermore, we demonstrated that EGFP transgene expression was retargeted to MT-2 by NDFL-EGFP via ·HN-IL-2 ex vivo and that virus hemadsorption was inhibited by ·HN-IL-2 in vivo (17). To prove the principle of virus retargeting in vivo, we first had to establish a model consisting of target-positive and target-negative tumor cell lines.…”

Section: Discussionmentioning

confidence: 76%

“…We have previously shown in vitro that, by doing so, a recombinant NDV could be retargeted selectively to marker-defined tumor cells (16,17). For this, we pre-incubate the virus with a specially designed recombinant bispecific fusion protein (·HN-IL-2).…”

Section: Introductionmentioning

confidence: 99%

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

Bian

Fournier²,

Peeters³

et al. 2005

Int J Oncol

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Abstract. Previously we have demonstrated that a recombinantBiodistribution 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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Newcastle Disease Virus: A Promising Vector for Viral Therapy, Immune Therapy, and Gene Therapy of Cancer

Schirrmacher

Fournier

2009

Gene Therapy of Cancer

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106

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This review deals with the avian paramyxovirus Newcastle disease virus (NDV) and describes properties that explain its oncolytic activity, its tumor-selective replication behavior, and its immune-stimulatory capacity with human cells. The strong interferon response of normal cells upon contact with NDV appears to be the basis for the good tolerability of the virus in cancer patients and for its immune stimulatory properties, whereas the weak interferon response of tumor cells explains the tumor selectivity of replication and oncolysis. Various concepts for the use of this virus for cancer treatment are pointed out and results from clinical studies are summarized. Reverse genetics technology has made it possible recently to clone the genome and to introduce new foreign genes thus generating new recombinant viruses. These can, in the future, be used to transfer new therapeutic genes into tumors and also to immunize against new emerging pathogens. The modular nature of gene transcription, the undetectable rate of recombination, and the lack of a DNA phase in the replication cycle make NDV a suitable candidate for the rational design of a safe and stable vaccine and gene therapy vector.

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Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein

Cited by 16 publications

References 42 publications

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

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

Newcastle Disease Virus: A Promising Vector for Viral Therapy, Immune Therapy, and Gene Therapy of Cancer

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