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

Janke, Markus; Peeters, Ben; Leeuw, Olav de; Moorman, R.; Arnold, Annette; Fournier, Philippe; Schirrmacher, Volker

doi:10.1038/sj.gt.3303026

Cited by 81 publications

(78 citation statements)

References 36 publications

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“…However, it is known that TRAIL can be upregulated also by IFN-α/β (51,52) and IFN-γ (52,53). Interestingly, we detected high concentrations of IFN-α/γ in response to rNDV stimulation; thus, we cannot exclude that part of soluble TRAIL measured in PBMC cultures comes from populations of monocytes and/or T-cells stimulated with type I IFNs, as it has been already reported (20,47).…”

Section: Discussioncontrasting

confidence: 42%

“…It is known that it provokes the release of danger signals during virus replication into the tumor cell cytoplasm (14)(15)(16) and stimulates the immune system to produce cytokines such as interferons (IFNs) or TNF (17). In turn, these inflammatory cytokines lead to the activation of natural killer (NK) cells, monocytes, macrophages and sensitized T cells, stimulating both innate and adaptive immune response (17)(18)(19)(20)(21).…”

Section: Antitumor and Immunostimulatory Activities Of A Genotype V Rmentioning

confidence: 99%

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Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

et al. 2017

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Abstract. Antitumor conventional treatments including chemo/radiotherapy result in several side effects and non-specificity. Therapies including the use of oncolytic viruses, particularly the Newcastle disease virus (NDV), have emerged as an attractive alternative due to their capacity to kill cancer cells directly or through stimulation of the immune system. In the present study, a commercial vaccine composed of a recombinant attenuated NDV strain P05 (rNDV-P05) was assessed for antitumor and immunostimulatory activity. Firstly, hemagglutination activity was evaluated at different pH and temperature conditions. Then, cancer cell lines and peripheral blood mononuclear cells (PBMC) were co-cultured with or without rNDV-P05 and cytoplasmic nucleosomes were measured by enzyme-linked immunosorbent assay (ELISA) as an apoptosis indicator. Antitumor cytokines produced by PBMC in response to the virus were analyzed by ELISA and reverse transcription quantitative polymerase chain reaction. Characterization of rNDV-P05 indicates that the virus is slightly sensible to acid and basic pH, and stable at temperatures no greater than 42˚C. The majority of cell lines developed apoptosis in co-culture with rNDV-P05 in a dose-time dependent manner. The highest level of HeLa, HCC1954 and HepG2 cell apoptosis was at 48 h/50 hemagglutination units (HU), and HL-60 was 24 h/50 HU. A549 cell line and PBMC did not show sensitivity to apoptosis by the virus. PBMC from healthy donors stimulated with the rNDV-P05 increased significantly the levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α and soluble TNF-related apoptosis-inducing ligand in culture supernatants, as well as their mRNA expression. These results demonstrate that the pro-apoptotic effect of rNDV-P05 and its magnitude is specific to particular tumor cell lines and is not induced on PBMC; and the virus stimulates the expression of several key antitumor cytokines. This study promotes the use of rNDV-P05 in an alternate application of different viral strains during virotherapy with NDV.

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Section: Discussioncontrasting

confidence: 42%

Section: Antitumor and Immunostimulatory Activities Of A Genotype V Rmentioning

confidence: 99%

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

et al. 2017

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“…While Ras is the main factor determining NDV tropism, mutations in the IFN signalling pathway also confer sensitivity to NDV. Live attenuated strains of NDV have shown efficacy in mouse models of fibroblastoma (Lorence et al, 1994a), neuroblastoma (Lorence et al, 1994b;Reichard et al, 1993), colon (Schulze et al, 2009), prostate (Phuangsab et al, 2001), melanoma (Zamarin et al, 2009), large cell lung (Phuangsab et al, 2001) and breast carcinoma (Zhao et al, 2008;Janke et al, 2007). Moreover, live attenuated NDV strains MTH-68/H and PV701 are currently in clinical trials for high-grade gliomas (HGG) and advanced solid cancer, respectively (Csatary et al, 2004;Pecora et al, 2002).…”

Section: Newcastle Disease Virusmentioning

confidence: 99%

Herpes Simplex Type 1 for Use in Cancer Gene Therapy: Looking Backward to Move Forward

Cuddington¹,

Mossman²

2011

Viral Gene Therapy

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“…19,20 Recently an NDV (strain LaSota) with a transgene encoding for granulocyte macrophage colony-stimulating factor (GM-CSF) as a vector for cancer immunogene therapy was described. 21 Although virulent strains of NDV were analogously generated as recombinant viruses like Beaudette C 22 and Herts 33, 23 no recombinant virus of strains that had been tested in patients and been shown to be safe in humans has yet been developed. For the mesogenic NDV strain Beaudette C, it was shown by Krishnamurthy et al 22 that insertion of a transgene results in growth retardation and attenuation of the virus.…”

Section: Introductionmentioning

confidence: 99%

Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes

et al. 2008

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The most advanced oncolytic Newcastle disease virus (NDV) strains that are used in clinical trials for the treatment of cancer are wild-type mesogenic strains. These virus strains have an inherent, nongenetically engineered, oncolytic activity and selectively replicate in tumor cells but not in normal human cells. To date no investigations have been performed with genetically engineered mesogenic NDV regarding the oncolytic activity. We describe here the generation of recombinant viruses of the mesogenic naturally oncolytic NDV strain MTH68. We show that not only one, but also two additional transgenes coding for amino-acid chains with a molecular weight of 25 and 50 kDa can be inserted into the viral genome without affecting viral growth, oncolytic potency or tumor-selective replication of the virus. Transgenic expression of the heavy and light chains of a monoclonal antibody, as separate additional transcriptional cassettes, leads to the expression of full immunoglobulin G (IgG) monoclonal antibody by recombinant NDV. Infection of tumor cells with antibody-transgenic viruses results in the efficient production and secretion of a functional full size IgG antibody by the tumor cells, that specifically binds to its target-antigen in tumor tissue. This approach will allow to combine the advantages of oncolytic RNA viruses and monoclonal antibodies in a single powerful anticancer agent with improved or even new therapeutic properties.

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

Cited by 81 publications

References 36 publications

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

Antitumor and immunostimulatory activities of a genotype V recombinant attenuated veterinary Newcastle disease virus vaccine

Herpes Simplex Type 1 for Use in Cancer Gene Therapy: Looking Backward to Move Forward

Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes

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