Velogenic Newcastle Disease Virus as an Oncolytic Virotherapeutics: In Vitro Characterization

Kumar, Rajiv; Tiwari, Ashok Kumar; Chaturvedi, Uttara; Kumar, Girish; Sahoo, Aditya Prasad; Rajmani, R. S.; Saxena, Lovleen; Saxena, Shikha; Tiwari, Sangeeta; Kumar, Satish

doi:10.1007/s12010-012-9700-1

Cited by 39 publications

(28 citation statements)

References 46 publications

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“…NDV has been demonstrated by Elankumaran et al to mediate its oncolytic effects by both intrinsic and extrinsic caspase-dependent pathways of cell death [31]. In another study, NDV-induced apoptosis was shown to be dependent on upregulation of TNF-related apoptosis-inducing ligand (TRAIL) and caspase activation [32]. This causes opening of mitochondrial permeability transition pores and loss of mitochondrial membrane potential, leading to a complex mechanism forming at the end the apoptosome, which is responsible for the activation of the apoptosis process [33].…”

Section: Ndv For Cancer Therapymentioning

confidence: 99%

Oncolytic Newcastle Disease Virus as Cutting Edge between Tumor and Host

Fournier

Schirrmacher

2013

Biology

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Oncolytic viruses (OVs) replicate selectively in tumor cells and exert anti-tumor cytotoxic activity. Among them, Newcastle Disease Virus (NDV), a bird RNA virus of the paramyxovirus family, appears outstanding. Its anti-tumor effect is based on: (i) oncolytic activity and (ii) immunostimulation. Together these activities facilitate the induction of post-oncolytic adaptive immunity. We will present milestones during the last 60 years of clinical evaluation of this virus. Two main strategies of clinical application were followed using the virus (i) as a virotherapeutic agent, which is applied systemically or (ii) as an immunostimulatory agent combined with tumor cells for vaccination of cancer patients. More recently, a third strategy evolved. It combines the strategies (i) and (ii) and includes also dendritic cells (DCs). The first step involves systemic application of NDV to condition the patient. The second step involves intradermal application of a special DC vaccine pulsed with viral oncolysate. This strategy, called NDV/DC, combines anti-cancer activity (oncolytic virotherapy) and immune-stimulatory properties (oncolytic immunotherapy) with the high potential of DCs (DC therapy) to prime naive T cells. The aim of such treatment is to first prepare the cancer-bearing host for immunocompetence and then to instruct the patient’s immune system with information about tumor-associated antigens (TAAs) of its own tumor together with danger signals derived from virus infection. This multimodal concept should optimize the generation of strong polyclonal T cell reactivity targeted against the patient’s TAAs and lead to the establishment of a long-lasting memory T cell repertoire.

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Section: Ndv For Cancer Therapymentioning

confidence: 99%

Oncolytic Newcastle Disease Virus as Cutting Edge between Tumor and Host

Fournier

Schirrmacher

2013

Biology

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“…[17][18][19][20][21][22][23][24] Several studies have demonstrated that increasing the virulence of recombinant NDV (rNDV) by editing the F protein cleavage site results in better oncolytic activity, but also in higher pathogenicity in chickens. [25][26][27] Surprisingly, detailed information on preclinical safety testing of oncolytic NDVs is scarce, and a comparison of different (non-)virulent strains in non-human primate models has never been described.…”

Section: Introductionmentioning

confidence: 99%

Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy

et al. 2014

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Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic potential. Detailed preclinical information regarding the safety of oncolytic NDV is scarce. In this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic NDVs in non-human primates (Macaca fascicularis). Two animals were injected with escalating doses of a non-recombinant vaccine strain, a recombinant lentogenic strain or a recombinant mesogenic strain. To study transmission, naive animals were co-housed with the injected animals. Injection with NDV did not lead to severe illness in the animals or abnormalities in hematologic or biochemistry measurements. Injected animals shed low amounts of virus, but this did not lead to seroconversion of the contact animals. Postmortem evaluation demonstrated no pathological changes or evidence of virus replication. This study demonstrates that NDV generated in embryonated chicken eggs is safe for intravenous administration to non-human primates. In addition, our study confirmed results from a previous report that naïve primate and human sera are able to neutralize egg-generated NDV. We discuss the implications of these results for our study and the use of NDV for virotherapy.

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“…On the other hand, NDV is non-pathogenic to humans and its oncotherapeutic benefits have been used in preclinical studies making it a promising non-conventional oncovirotherapeutic agent (6). NDV is as highly suitable as an oncolytic agent and is also considered a potential agent in the treatment of cancer as it selectively kills tumor cells (7).…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis in MCF-7 cells by the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus Malaysian strain AF2240

et al. 2013

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Newcastle disease virus (NDV) exerts its naturally occurring oncolysis possibly through the induction of apoptosis. We hypothesized that the binding of the virus to the cell via the hemagglutinin-neuraminidase (HN) glycoprotein may be sufficient to not only induce apoptosis but to induce a higher apoptosis level than the parental NDV AF2240 virus. NDV AF2240 induction of apoptosis in MCF-7 human breast cancer cells was analyzed and quantified. In addition, the complete HN gene of NDV strain AF2240 was amplified, sequenced and cloned into the pDisplay eukaryotic expression vector. HN gene expression was first detected at the cell surface membrane of the transfected MCF-7 cells. HN induction of apoptosis in transfected MCF-7 cells was analyzed and quantified. The expression of the HN gene alone was able to induce apoptosis in MCF-7 cells but it was a less potent apoptosis inducer compared to the parental NDV AF2240 strain. In conclusion, the NDV AF2240 strain is a more suitable antitumor candidate agent than its recombinant HN gene unless the latter is further improved by additional modifications.

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Velogenic Newcastle Disease Virus as an Oncolytic Virotherapeutics: In Vitro Characterization

Cited by 39 publications

References 46 publications

Oncolytic Newcastle Disease Virus as Cutting Edge between Tumor and Host

Oncolytic Newcastle Disease Virus as Cutting Edge between Tumor and Host

Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy

Induction of apoptosis in MCF-7 cells by the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus Malaysian strain AF2240

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