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.

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 Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Teridah Ernala Ginting ◽  
Salomo Christian ◽  
Young Othiwi Larasati ◽  
Jeremiah Suryatenggara ◽  
Ivet Marita Suriapranata ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Protein A ◽  
Cumulative Effect ◽  
Enzyme Activation ◽  
Type I ◽  
Type I Ifn ◽  
Normal Cells

Abstract Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-α/-β and IFN-λ, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activation and annexin-V detection. The apoptosis response was inhibited by B18R protein (a type I IFN inhibitor) in tumor cells i.e. A549 and U87MG, and not in normal cells i.e. NB1RGB and HEK293. Similarly, UV-inactivated medium from NDV infection was shown to induce apoptosis in corresponding cells and the response was inhibited in A549 and U87MG cells with the addition of B18R protein. Treatment with combination of IFNs-α/-β/-λ or IFNs-α/-β or IFN-λ in NB1RGB, HEK293, A549 and U87MG showed that caspase activity in IFNs-α/-β/-λ group was the highest, followed with IFN-α/-β group and IFN-λ group. This suggests that tumor-selectivity of NDV is mainly because of the cumulative effect of type I and III in tumor cells that lead to higher apoptotic effect.

Newcastle Disease Virus V protein interacts with hnRNP H1 to promote viral replication

2021 ◽  
pp. 109093
Author(s):  
Lina Tong ◽  
Zhili Chu ◽  
Xiaolong Gao ◽  
Mengqing Yang ◽  
Fathalrhman Eisa A. Adam ◽  
...  
Keyword(s):  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
V Protein

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.

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