Genetically engineered Newcastle disease virus expressing interleukin-2 and TNF-related apoptosis-inducing ligand for cancer therapy

Bai, Fuliang; Yu, Yin-Hang; Tian, Hui; Ren, Guangxin; Wang, Hui; Zhou, Bing; Han, Xiaohui; Yu, Qingzhong; Li, Deshan

doi:10.4161/cbt.29686

Cited by 77 publications

(61 citation statements)

References 45 publications

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“…IL2 is the only one approved by the Food and Drug Administration (FDA) for the treatment of cancer [10, 11]. More importantly, many studies proved that recombinant NDVs (rNDVs) expressing IL2 are promising anti-tumor agents [12]. Therefore, IL2 has been demonstrated as a powerful foreign gene for elevating the anti-tumor effects of rNDVs.…”

Section: Introductionmentioning

confidence: 99%

Identification of Optimal Insertion Site in Recombinant Newcastle Disease Virus (rNDV) Vector Expressing Foreign Gene to Enhance Its Anti-Tumor Effect

Pan

Rasoul

et al. 2016

PLoS ONE

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Recombinant Newcastle disease virus (rNDV) is tumor selective and intrinsically oncolytic, which has been developed as a vector to express exogenous genes to enhance its oncolytic efficacy. Our previous studies found that insertion sites of foreign gene in rNDV vector affected its expression and anti-tumor activities. However, the optimal insertion site for foreign genes remains unknown. In this study, we inserted the enhanced green fluorescence protein (EGFP) and IL2 genes into four different intergenic regions of the rNDV using reverse genetics technology. Recombinants rNDV-EGFPs and rNDV-IL2s were successfully rescued, which displayed the similar growth kinetics with parental virus. Both EGFP mRNA and protein levels were most abundant in HepG2 cells, when EGFP gene was inserted between the NP/P site of the rNDV. Similarly, the IL-2 expressed by HepG2 cells infected with rNDV-IL2 was highest, when IL2 was inserted into NP/P site. To test whether these rNDVs that express higher foreign genes could induce stronger anti-tumor response, we treated the H22-oxter-tumor-bearing C57BL/6J mice with rNDV-IL2s and then examined the oncolytic efficacy. The results showed that rNDV-IL2-NP/P had the strongest inhibition of murine hepatoma carcinoma tumors. The splenocytes isolated from the mice treated with rNDV-IL2-NP/P reached the highest degrees of CD4+ T and CD8+ T cells. In addition, animals’ survival rate in rNDV-IL2-NP/P-treated group was higher than that of other groups. Taken together, these results demonstrate that NP and P gene junction in rNDV is the optimal insertion site for foreign genes expression to enhance rNDV’s anti-tumor effects.

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Section: Introductionmentioning

confidence: 99%

Identification of Optimal Insertion Site in Recombinant Newcastle Disease Virus (rNDV) Vector Expressing Foreign Gene to Enhance Its Anti-Tumor Effect

Pan

Rasoul

et al. 2016

PLoS ONE

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“…To increase apoptotic potential different strategies have been explored such as recombinant NDV strains expressing various cytokines such as interleukins, tumor necrosis factorrelated apoptosis inducing ligand and GM-CSF. 31,32 Virotherapy is one of the promising ways to treat cancer with low cytotoxicity and meager chance of relapse.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of an apoptotic strain of Newcastle disease virus isolated from an outbreak in India

Kumar

2015

Cancer Gene Ther

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Newcastle disease (ND) is a highly contagious disease of poultry. The ND virus (NDV) encodes an error-prone RNA-dependent RNA polymerase which can cause high mutation rate leading to the emergence of its new antigenic variants. Antigenic difference of NDV strains may result in massive outbreak in vaccinated and unvaccinated poultry flocks around the globe. Apart from its pathogenic potential NDV has been explored as an oncolytic agent for a broad range of human cancers. In the present study, we isolated a novel NDV strain from an outbreak in chicken flock from the eastern part of India. Molecular characterization showed the NDV strain to be virulent in nature. The complete genome sequence analysis of the newly isolated strains belongs to genotype XIII. Moreover, the newly isolated strain of NDV showed positive results in various apoptotic assays in human breast cancer cells, MCF-7. The study will be useful to explore the possibility of using a newly isolated strain of NDV for virotherapy.

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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%

“…The rescue procedure for obtaining the recombinant virus has been established in our laboratory. [14][15][16] All recombinant viruses were grown in embryonated SPF eggs. The rescued viruses were named rClone30-IL-2, rClone30-IL-12, and rClone30-IL-12-IL-2, respectively.…”

Section: Plasmids and Cell Linesmentioning

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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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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Genetically engineered Newcastle disease virus expressing interleukin-2 and TNF-related apoptosis-inducing ligand for cancer therapy

Cited by 77 publications

References 45 publications

Identification of Optimal Insertion Site in Recombinant Newcastle Disease Virus (rNDV) Vector Expressing Foreign Gene to Enhance Its Anti-Tumor Effect

Identification of Optimal Insertion Site in Recombinant Newcastle Disease Virus (rNDV) Vector Expressing Foreign Gene to Enhance Its Anti-Tumor Effect

Molecular characterization of an apoptotic strain of Newcastle disease virus isolated from an outbreak in India

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

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