Recombinant Newcastle disease virus expressing human interleukin-2 serves as a potential candidate for tumor therapy

Zhao, Heng; Janke, Markus; Fournier, Philippe; Schirrmacher, Volker

doi:10.1016/j.virusres.2008.04.020

Cited by 57 publications

(50 citation statements)

References 26 publications

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“…Promising results were noted in multiple models of murine or human cancers using different strains of NDV. [8][9][10][11][12][13][14][15][16] In this study, we chose the NDV lentogenic strain Clone30 which is safe to avian species (not cause serious disease) as the parental skeleton to construct the recombinant viruses. The shortcoming of Clone30 is that the cell lysis ability is inferior to velogenic and mesogenic strains.…”

Section: Resultsmentioning

confidence: 99%

“…3,5,8 The development of reverse genetics technology for NDV enable us to modify the NDV genome as well as introduce foreign sequences to refine the antitumor activity. [9][10][11][12][13] Previous studies in our laboratory showed that recombinant NDVs (rNDVs) expressing Trail, interleukin (IL) 15, and IL-2 are promising antitumor agents. [14][15][16] Other reports also showed that rNDVs carrying granulocyte-macrophage colony-stimulating factor and tumor necrosis factor a were significantly enhanced with the antitumor efficacy compared to parental virus.…”

Section: Introductionmentioning

confidence: 99%

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Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Ren

Tian

Liu

et al. 2016

Technol Cancer Res Treat

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Interleukins as immunomodulators are promising therapeutic agents for cancer therapy. Previous studies showed that there was an improved antitumor immunity in tumor-bearing mice using recombinant Newcastle disease virus carrying for interleukin-2. Interleukin-12 is a promising antitumor cytokine too. So we investigated and compared the antitumor effect of genetically engineered Newcastle disease virus strains expressing both interleukin-12 and/or interleukin-2 (rClone30-interleukin-2, rClone30-interleukin-12, and rClone30-interleukin-12-interleukin-2). In vitro studies showed that rClone30s could efficiently infect tumor cells and express interleukin-12 and/or interleukin-2. 3-(4,5-Dimethylthiazol-2-y)-2,5-diphenyl-tetrazolium bromide results showed rClone30s possessed strong cytotoxic activities against multiple tumor cell lines (U251, HepG2, A549, and Hela). Animal studies showed that rClone30-interleukin-12-interleukin-2 was more effective in inhibition of murine hepatoma carcinoma tumors, with the mean tumor volume (day 14) of 141.70 mm 3 comparing 165.67 mm 3 of rClone30-interleukin-12 group, 210.47 mm 3 of rClone30-interleukin-2 group, 574.70 mm 3 of rClone30 group, and 1206.83 mm 3 of phosphate-buffered saline group. Moreover, the rClone30-interleukin-12-interleukin-2 treated mice secreted more interferon g (333.518 pg/mL) and its downstream cytokine interferon-g induced protein 10 (16.006 pg/mL) in tumor than the rClone30-interleukin-12 group (interferon g: 257.548 pg/mL; interferon-g induced protein 10: 13.601 pg/mL), rClone30-interleukin2 group (interferon g: 124.601 pg/mL; interferon-g induced protein 10: 9.779 pg/mL), or rClone30 group (interferon g: 48.630 pg/mL; interferon-g induced protein 10:1.650 pg/mL). For the survival study, rClone30-interleukin12-interleukin2 increased the survival rate (12 of 16) of the tumor-bearing mice versus 11 of 16 in rClone30-interleukin-12 group, 10 of 16 in rClone30-interleukin-2 group, 7 of 16 in Clone30 group, and 0/16 in phosphate-buffered saline group, respectively. To determine whether the mice treated with recombinant virus developed protective immune response, the mice were rechallenged with the same tumor cells. The results showed that viral-treated mice were significantly protected from rechallenge. These results suggest that expressing both interleukin-2 and/or interleukin-12 could be ideal approaches to enhance the antitumor ability of Newcastle disease virus, and rClone30-interleukin-12-interleukin-2 is slightly superior over rClone30-interleukin-12 and rClone30-interleukin-2 alone.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Ren

Tian

Liu

et al. 2016

Technol Cancer Res Treat

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“…Viruses with inherent oncolytic properties can be used as new therapeutic agents (3,33). They can also be used as vectors for cancer gene therapy (34,35). The proper targeting of tumor tissue by viruses is, however, still a major problem.…”

Section: Discussionmentioning

confidence: 99%

“…We performed some pilot in vivo experiments of NDV hitchhiking with iPEC cells. The cells were loaded with either oncolytic MTH-68 virus or with recombinant NDV producing GM-CSF (34) or IL-2 (35). Some ESb tumor-bearing mice treated with NDV loaded iPEC were seen which survived much longer than mice treated with iPEC without virus (Schirrmacher, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus

Pfirschke

Schirrmacher²

2009

Int J Oncol

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Abstract. Oncolytic virotherapy, a new type of cancer therapy involving viruses with oncolytic and immunostimulatory potential, is based on tumor selective viral replication, resulting in a specific lysis of tumor cells. Effective tumor targeting of oncolytic viruses remains a major problem because only a fraction of systemically applied viruses can reach the tumor tissue. We describe for the first time in an in vitro co-culture system that T lymphocytes can be loaded with Newcastle disease virus (NDV) in such a way that the virus load will be transferred to the tumor target cells upon contact of the T cells with tumor cells. The effectiveness of this NDV 'hitchhiking' on T cells can be influenced by the amount of virus, the ratio of T cells to tumor cells, the activation status of the T cells and by the virulence of the virus as shown by flow cytometry, quantitative real-time PCR and fluorescence microscopy. In a tumor neutralization assay in vitro, monolayers of human tumor cells could be completely and effectively destroyed by the addition of polyclonally activated human T cells loaded with oncolytic NDV. This process involves the formation of large T cell clusters as revealed by phase-contrast microscopy. Loading of oncolytic NDV onto activated T cells and adoptive transfer into a tumor-bearing host might enhance the efficacy of adoptive T cell therapy of tumors as well as tumor targeting of oncolytic viruses.

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“…Over the last years, reverse genetics has allowed to modify the RNA genome of this virus. Following such procedures, we produced the following NDV recombinant viruses with transgenes coding for enhanced green fluorescent protein (EGFP) (5,6), interleukin-2 (IL-2) (7,8) or granulocyte macrophage colony stimulating factor (GM-CSF) (9).…”

Section: Introductionmentioning

confidence: 99%

Importance of retinoic acid-inducible gene I and of receptor for type I interferon for cellular resistance to infection by Newcastle disease virus

Fournier

Wilden²,

Schirrmacher

2011

Int J Oncol

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Abstract. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic properties which shows promising effects in the treatment of cancer. Anti-cancer effects are due to the virus ability: i) to replicate in and kill tumor cells, leading finally to their selective elimination; and ii) to induce the stimulation of antitumor activities in immune cells. NDV does not harm normal cells and has a high safety profile. In this study, we first report a direct correlation between the degree of cell resistance to NDV infection and the cellular expression of the retinoic acid-inducible gene I (RIG-I) which is a cytosolic viral RNA receptor. RIG-I plays an important role in the recognition of and response to infection by RNA viruses. We also demonstrate that impairment of the interferon (IFN) pathway through deletion of the receptor for type I IFN (IFNR1) in primary macrophages leads to NDV replication. In tumor cells, addition of exogenous IFN-α4 is shown to lead to tumor growth reduction and inhibition of viral replication. Finally, increase of the RIG-I concentration of tumor cells via plasmid transfection is shown to be associated with a stronger resistance to NDV infection. These findings shed new light on the crucial role played by the cytosolic receptor RIG-I and the plasma membrane receptor IFNR1 as key molecules to protect cells against infection by NDV.

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Recombinant Newcastle disease virus expressing human interleukin-2 serves as a potential candidate for tumor therapy

Cited by 57 publications

References 26 publications

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus

Importance of retinoic acid-inducible gene I and of receptor for type I interferon for cellular resistance to infection by Newcastle disease virus

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