Expressing foreign genes by Newcastle disease virus for cancer therapy

Bai, Fuliang; Tian, Hui; Yu, Qingzhong; Ren, Guangxin; Li, D. S.

doi:10.1134/s0026893315020028

Cited by 4 publications

(5 citation statements)

References 59 publications

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“…Its genome can stably express foreign gene; and the expression level of a foreign gene can be affected by the insertion region [18, 19]. However, the optimal insertion site for foreign gene expression to increase rNDV’s anti-tumor efficacy remains elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we used H22 oxter tumor-bearing mice model to evaluate expression levels of IL2 and its anti-tumor efficacy in vivo . The results indicated that rNDV/IL2s significantly inhibited tumor growth with more than 92% inhibition rate compared with rNDV- and PBS-treated groups [18]. Although there was no significant difference, mice treated with rNDV-IL2-NP/P had a little higher tumor regression and exhibited higher survival rate than the other rNDV-treated groups.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…Only a few NDVs have entered clinical trials, and none have been used in clinical practice. However, significant antitumor activity, selective replication in malignant cells, and low toxicity in human normal human cells 20,[31][32][33] have raised scientists' greatstimulated interest in the oncolytic effects of NDV.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic Activity of Wild-type Newcastle Disease Virus HK84 Against Hepatocellular Carcinoma Associated with Activation of Type I Interferon Signaling

Chen

Niu

Sun

et al. 2021

J Clin Transl Hepatol

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“…Interleukin (IL)-2 is a pleiotropic cytokine which exerts important effects on cells of the innate and adaptive immune systems (4). IL-2 was the first effective immunotherapeutic approved by the US Food and Drug Administration for metastatic melanoma (5), and is involved in T-cell activation and effector functions, including T-cell proliferation, interferon (IFN)-γ production and cytotoxicity (6).…”

Section: Introductionmentioning

confidence: 99%

The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma

Qiao

et al. 2018

Mol Med Report

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Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model. In addition, the activity of IL‑2 was analyzed. The antitumor potential of IL‑2 and rAd‑p53 was studied using xenograph mice carrying GBM cells. Tumor‑specific CD4+ and CD8+ T cells were also analyzed in the GBM‑bearing models. The results demonstrated that IL‑2 and rAd‑p53 not only stimulated tumor‑specific cytotoxic T‑lymphocyte responses and increased regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally increased expression of apoptosis‑associated genes. The treatment with IL‑2 and rAd‑p53 resulted in tumor regression and prolonged the survival of glioma‑bearing mice. Taken together, a combination of IL‑2 and rAd‑p53 treatment combines the effects of immunotherapy and oncolytic therapy and may be a comprehensive therapeutic schedule for clinical application in future cancer therapies.

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Expressing foreign genes by Newcastle disease virus for cancer therapy

Cited by 4 publications

References 59 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

Oncolytic Activity of Wild-type Newcastle Disease Virus HK84 Against Hepatocellular Carcinoma Associated with Activation of Type I Interferon Signaling

The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma

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