Recombinant Newcastle disease virus expressing P53 demonstrates promising antitumor efficiency in hepatoma model

An, Ying; Liu, Tianyan; He, Jinjiao; Wu, Huijun; Chen, Rui; Liu, Yunye; Wu, Yunjie; Yin, Bo; Guo, Xiaochen; Zheng, Qi; Liu, Chang; Yin, Jun; Li, Deshan; Ren, Guangxin

doi:10.1186/s12929-016-0273-0

Cited by 19 publications

(21 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current trend is to use recombinant strains with decreased pathogenicity and improved antitumor effect [ 21 – 26 ]. However, naturally occurring oncolytic NDV strains are also observed.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model

et al. 2018

View full text Add to dashboard Cite

Oncolyic virotherapy is one of the modern experimental techniques to treat human cancers. Here we studied the antitumor activity of wild-type Newcastle disease virus (NDV) isolates from Russian migratory birds. We showed that NDV could selectively kill malignant cells without affecting healthy cells. We evaluated the oncolytic effect of 44 NDV isolates in 4 histogenetically different human cell lines (HCT116, HeLa, A549, MCF7). The safety of the isolates was also tested in normal peripheral blood mononuclear (PBMC) cells. The viability of tumor cell lines after incubation with NDV isolates was evaluated by MTT. All cell lines, except for normal PBMC primary cells, had different degrees of susceptibility to NDV infection. Seven NDV strains had the highest oncolytic activity, and some NDV strains demonstrated oncolytic selectivity for different cell lines. In vivo, we described the intratumoral activity of NDV/Altai/pigeon/770/2011 against subcutaneous non-small cell lung carcinoma using xenograft SCID mice model. All animals were responsive to therapy. Histology confirmed therapy-induced destructive changes and growing necrotic bulk density in tumor tissue. Our findings indicate that wild-type NDV strains selectively kill tumor cells with no effect on healthy PBMC cells, and intratumoral virotherapy with NDV suppresses the subcutaneous tumor growth in SCID mice.

show abstract

Section: Introductionmentioning

confidence: 99%

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model

et al. 2018

View full text Add to dashboard Cite

show abstract

“…WT p53 transgenes also increased cytotoxicity of two other OVs, VSV and NDV 48, 54, 61, 67. In our recent study, VSV-p53 showed enhanced killing of the pancreatic cancer cell line SUIT2 compared with VSV not expressing p53 when these viruses were tested at a low MOI 67 .…”

Section: Main Textmentioning

confidence: 76%

“…Other OVs armed with a p53 transgene were demonstrated to be safe in animals, including Newcastle disease virus (NDV; a paramyxovirus) 61 and various recombinant VSVs 62 . Toxicity studies in mice showed that after 10 systemic injections of rNDV-p53 (1 × 10 7 PFU each), the serum from mice showed no changes in serum creatinine, aspartate transaminases, alanine transaminases, or blood urea nitrogen levels, supporting the safety of that virus 61 .…”

Section: Main Textmentioning

confidence: 99%

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

Bressy

Hastie

Grdzelishvili

2017

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

show abstract

“…NDV has been used to treat neuroblastoma, melanoma, and other malignancies. Previous studies have reported that the tumor volume is substantially decreased after NDV infection …”

Section: Discussionmentioning

confidence: 95%

Recombinant Newcastle disease virus expressing human IFN‐λ1 (rL‐hIFN‐λ1)‐induced apoptosis of A549 cells is connected to endoplasmic reticulum stress pathways

Yan

Liu

et al. 2018

Thoracic Cancer

View full text Add to dashboard Cite

BackgroundIFN‐λs are a kind of cytokine with anti‐tumor, immunomodulatory, and anti‐proliferative activity. Recent studies have shown that the recombinant Newcastle disease virus expresses human IFN‐λ1 (rL‐hIFN‐λ1), which plays a role in gastric cancer cell apoptosis. Endoplasmic reticulum stress (ERS) induces autophagy and apoptosis in tumor cells. In this study, we explored the relationship between ERS and rL‐hIFN‐λ1‐induced apoptosis of lung adenocarcinoma A549 cells and its underlying mechanism.MethodsFirst, we investigated the effect of rL‐hIFN‐λ1 on cellular proliferation, migration, and proteins associated with ERS, autophagy, and apoptosis of A549. Second, after administration of the ERS inhibitor, the associated proteins induced by rL‐hIFN‐λ1 were detected. Finally, a subcutaneous mouse model was used to examine the effect of rL‐hIFN‐λ1 on tumor growth and the ERS and apoptosis associated proteins in tumor tissues.ResultsThe results showed that the proliferation and migration of A549 cells, and tumor tissue growth were significantly inhibited and the ERS, autophagy, and apoptosis associated proteins were upregulated in the experimental group. Additionally, both 4‐PBA and knockdown of PERK or CHOP reduced the levels of rL‐hIFN‐λ1‐induced autophagy and apoptosis‐associated proteins. BCL‐2 knockdown caused autophagy and apoptosis associated protein upregulation.ConclusionsIn summary, rL‐hIFN‐λ1 inhibited cell proliferation and activated ERS, autophagy, and apoptosis in A549 cells and tissues, and when ERS pathways were blocked, the inhibiting effect was even more pronounced. Therefore, the recombinant Newcastle disease virus rL‐hIFN‐λ1‐induced apoptosis of A549 cells is connected to ER stress and could be a promising therapeutic agent for lung adenocarcinoma.

show abstract

Recombinant Newcastle disease virus expressing P53 demonstrates promising antitumor efficiency in hepatoma model

Cited by 19 publications

References 42 publications

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

Recombinant Newcastle disease virus expressing human IFN‐λ1 (rL‐hIFN‐λ1)‐induced apoptosis of A549 cells is connected to endoplasmic reticulum stress pathways

Contact Info

Product

Resources

About