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

Walter, Robert; Attar, Bashar M.; Lakshminarayan, Sooraj Tk; Rafiq, Asad; Delimata, Megan

doi:10.1016/s0016-5085(10)62095-1

Cited by 12 publications

(15 citation statements)

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“…This suggests that virus replication itself is a critical factor for NDV-induced cytotoxicity, as was described in earlier studies in other cells. [9][10][11][12][13]19,[32][33][34][35] This would argue for increasing the fusogenicity of an optimized recombinant NDV for treatment of pancreatic tumors. We observed multicycle replication of a lentogenic strain of NDV in some HPACs without addition of exogenous trypsin.…”

Section: Discussionmentioning

confidence: 99%

Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection

Eijck

et al. 2014

Cancer Gene Ther

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Newcastle disease virus (NDV) is a naturally occurring oncolytic virus with clinically proven efficacy against several human tumor types. Selective replication in and killing of tumor cells by NDV is thought to occur because of differences in innate immune responses between normal and tumor cells. In our effort to develop oncolytic virotherapy with NDV for patients with pancreatic cancer, we evaluated the responses to NDV infection and interferon (IFN) treatment of 11 different established human pancreatic adenocarcinoma cell lines (HPACs). Here we show that all HPACs were susceptible to NDV. However, this NDV infection resulted in different replication kinetics and cytotoxic effects. Better replication resulted in more cytotoxicity. No correlation was observed between defects in the IFN pathways and NDV replication or NDV-induced cytotoxicity. IFN production by HPACs after NDV infection differed substantially. Pretreatment of HPACs with IFN resulted in diminished NDV replication and decreased the cytotoxic effects in most HPACs. These findings suggest that not all HPACs have functional defects in the innate immune pathways, possibly resulting in resistance to oncolytic virus treatment. These data support the rationale for designing recombinant oncolytic NDVs with optimized virulence that should likely contain an antagonist of the IFN pathways.

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Section: Discussionmentioning

confidence: 99%

Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection

Eijck

et al. 2014

Cancer Gene Ther

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“…The titer of the virus was determined using Embryo Infectious Dose 50 (EID50). In order to inactivate NDV, the sample was exposed to the UV radiation [17] and the result was confirmed by Vero cell line [18,19]. The finding revealed that the UV-inactivated NDV does not create any plaques in Vero cells.…”

Section: Virus and Cell Linesmentioning

confidence: 92%

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

Keshavarz

Ebrahimzadeh

Miri

et al. 2020

Virol J

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Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and-9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). Results: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.

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“…The Newcastle disease virus has been proposed as a promising therapeutic agent because of its ability to preferentially kill cancer cells [ 5 ]. Previous published data have shown the oncolytic potential of LaSota strain wild type or genetically modified in solid tumors in vitro [ 30 , 31 , 32 ]. A genetically modified LaSota strain has been tested in leukemic blasts and myeloma cell lines [ 4 , 33 ], but, to our knowledge, there is no information about the use of lentiviral strains in aggressive lymphomas…”

Section: Discussionmentioning

confidence: 99%

Newcastle Disease Virus: Potential Therapeutic Application for Human and Canine Lymphoma

Sánchez

Pelayo

Medina

et al. 2015

Viruses

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Research on oncolytic viruses has mostly been directed towards the treatment of solid tumors, which has yielded limited information regarding their activity in hematological cancer. It has also been directed towards the treatment of humans, yet veterinary medicine may also benefit. Several strains of the Newcastle disease virus (NDV) have been used as oncolytics in vitro and in a number of in vivo experiments. We studied the cytolytic effect of NDV-MLS, a low virulence attenuated lentogenic strain, on a human large B-cell lymphoma cell line (SU-DHL-4), as well as on primary canine-derived B-cell lymphoma cells, and compared them to healthy peripheral blood mononuclear cells (PBMC) from both humans and dogs. NDV-MLS reduced cell survival in both human (42% ± 5%) and dog (34% ± 12%) lymphoma cells as compared to untreated controls. No significant effect on PBMC was seen. Cell death involved apoptosis as documented by flow-cytometry. NDV-MLS infections of malignant lymphoma tumors in vivo in dogs were confirmed by electron microscopy. Early (24 h) biodistribution of intravenous injection of 1 × 1012 TCID50 (tissue culture infective dose) in a dog with T-cell lymphoma showed viral localization only in the kidney, the salivary gland, the lung and the stomach by immunohistochemistry and/or endpoint PCR. We conclude that NDV-MLS may be a promising agent for the treatment of lymphomas. Future research is needed to elucidate the optimal therapeutic regimen and establish appropriate biosafety measures.

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

Cited by 12 publications

References 0 publications

Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection

Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

Newcastle Disease Virus: Potential Therapeutic Application for Human and Canine Lymphoma

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