Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence

2006 ◽  
Vol 119 (2) ◽  
pp. 328-338 ◽  
Author(s):  
Christoph Fiola ◽  
Ben Peeters ◽  
Philippe Fournier ◽  
Annette Arnold ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Tumor Selective

scholarly journals Type I Interferon-Sensitive Recombinant Newcastle Disease Virus for Oncolytic Virotherapy

2010 ◽  
Vol 84 (8) ◽  
pp. 3835-3844 ◽  
Author(s):  
Subbiah Elankumaran ◽  
Vrushali Chavan ◽  
Dan Qiao ◽  
Raghunath Shobana ◽  
Gopakumar Moorkanat ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Human Cells ◽  
Type I ◽  
V Protein ◽  
Normal Human ◽  
Normal Human Cells ◽  
Tumor Selective

ABSTRACT Newcastle disease virus (NDV), an avian paramyxovirus, is tumor selective and intrinsically oncolytic because of its potent ability to induce apoptosis. Several studies have demonstrated that NDV is selectively cytotoxic to tumor cells but not normal cells due to defects in the interferon (IFN) antiviral responses of tumor cells. Many naturally occurring strains of NDV have an intact IFN-antagonistic function and can still replicate in normal human cells. To avoid potential toxicity issues with NDV, especially in cancer patients with immunosuppression, safe NDV-oncolytic vectors are needed. We compared the cell killing abilities of (i) a recombinant NDV (rNDV) strain, Beaudette C, containing an IFN-antagonistic, wild-type V protein (rBC), (ii) an isogenic recombinant virus with a mutant V protein (rBC-Edit virus) that induces increased IFN in infected cells and whose replication is restricted in normal human cells, and (iii) a recombinant LaSota virus with a virulent F protein cleavage site that is as interferon sensitive as rBC-Edit virus (LaSota V.F. virus). Our results indicated that the tumor-selective replication of rNDV is determined by the differential regulation of IFN-α and downstream antiviral genes induced by IFN-α, especially through the IRF-7 pathway. In a nude mouse model of human fibrosarcoma, we show that the IFN-sensitive NDV variants are as effective as IFN-resistant rBC virus in clearing the tumor burden. In addition, mice treated with rNDV exhibited no signs of toxicity to the viruses. These findings indicate that augmentation of innate immune responses by NDV results in selective oncolysis and offer a novel and safe virotherapy platform.

scholarly journals Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Seyed Mohammad Miri ◽  
Mir Saeed Ebrahimzadeh ◽  
Elahe Abdolalipour ◽  
Mahsa Yazdi ◽  
Hassan Hosseini Ravandi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Gene Therapy ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Oncolytic Viruses

Abstract Background Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. Methods For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. Results The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8+ T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. Conclusions The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer.

scholarly journals Exosomes Carry microRNAs into Neighboring Cells to Promote Diffusive Infection of Newcastle Disease Virus

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 527 ◽  
Author(s):  
Changluan Zhou ◽  
Lei Tan ◽  
Yingjie Sun ◽  
Xusheng Qiu ◽  
Chunchun Meng ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Hela Cells ◽  
Newcastle Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Infections ◽  
Bioactive Substances ◽  
Cytopathic Effects

Newcastle disease virus (NDV), an avian paramyxovirus, was shown to prefer to replicate in tumor cells instead of normal cells; however, this mechanism has not been fully elucidated. Exosomes play a crucial role in intercellular communication due to the bioactive substances they carry. Several studies have shown that exosomes are involved in virus infections. However, the effect that exosomes have on NDV-infected tumor cells is not known. In this study, we focus on the role of exosomes secreted by NDV-infected HeLa cells in promoting NDV replication. Three miRNA candidates (miR-1273f, miR-1184, and miR-198) embraced by exosomes were associated with enhancing NDV-induced cytopathic effects on HeLa cells. Furthermore, luciferase assays, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA) all demonstrated that these miRNAs could suppress interferon (IFN)-β gene expression. Enhanced NDV replication in HeLa cells was identified by Western blot and plaque assays. Based on these results, we speculate that NDV employed exosomes entry into neighboring cells, which carry miRNAs, resulting in inhibition of the IFN pathway and promotion of viral infection. To our knowledge, this is the first report on the involvement of NDV-employed exosomes in tumor cells, and as such, it provides new insights into the development of anti-tumor therapies.

scholarly journals Tumor Cells Modified with Newcastle Disease Virus Expressing IL-24 as a Cancer Vaccine

2019 ◽  
Vol 14 ◽  
pp. 213-221 ◽  
Author(s):  
Xiaojing Xu ◽  
Cheng Yi ◽  
Xiaoqin Yang ◽  
Jianwei Xu ◽  
Qing Sun ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Cancer Vaccine ◽  
Newcastle Disease

scholarly journals M1986 Newcastle Disease Virus Lasota Strain Kills Human Pancreatic Cancer Tumor Cells In Vitro With High Selectivity

2010 ◽  
Vol 138 (5) ◽  
pp. S-453 ◽  
Author(s):  
Robert J. Walter ◽  
Bashar M. Attar ◽  
Sooraj TK Lakshminarayan ◽  
Asad Rafiq ◽  
Megan Delimata
Keyword(s):  
Pancreatic Cancer ◽  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
High Selectivity ◽  
Human Pancreatic Cancer ◽  
Cancer Tumor
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