Oncolytic Newcastle Disease Virus for Cancer Therapy: Old Challenges and New Directions

Zamarin, Dmitriy; Palese, Peter

doi:10.2217/fmb.12.4

Cited by 206 publications

(203 citation statements)

References 168 publications

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“…However, the fact that the pancreas is not considered a typical replication site for IAVs in humans, the modest replication level displayed by the H7N3 NS1-77 virus in mammalian non-malignant cells together with its administration in a confined space should enhance the safety of the potential treatment. Furthermore, rapid accumulation of virus-neutralizing antibodies in recipients has been reported also in the case of treatment with viruses that normally do not infect humans (Tesfay et al, 2014;Zamarin & Palese, 2012), and indeed one of the biggest challenges for OVs consists in eluding the adaptive immunity that might undermine their efficacy especially in a multi-dose regimen (Miest et al, 2011;Russell et al, 2012).…”

Section: The Immunostimulatory Activity Of H7n3 Ns1-77 Virus In Infecmentioning

confidence: 99%

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

Pizzuto

Silic-Benussi

Ciminale

et al. 2016

Journal of General Virology

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Pancreatic ductal adenocarcinoma (PDA) is one of the leading causes of cancer-related deaths worldwide and the development of new treatment strategies for PDA patients is of crucial importance. Virotherapy uses natural or engineered oncolytic viruses (OVs) to selectively kill tumour cells. Due to their genetic heterogeneity, PDA cells are highly variable in their permissiveness to various OVs. The avian influenza A virus (IAV) H7N3 A/turkey/Italy/2962/03 is a potent inducer of apoptosis in PDA cells previously shown to be resistant to other OVs (Kasloff et al., 2014), suggesting that it might be effective against specific subclasses of pancreatic cancer. To improve the selectivity of the avian influenza isolate for PDA cells, here confirmed deficient for IFN response, we engineered a truncation in the NS1 gene that is the major virusencoded IFN antagonist. The recombinant virus (NS1-77) replicated efficiently in PDA cells, but was attenuated in non-malignant pancreatic ductal cells, in which it induced a potent IFN response that acted upon bystander uninfected cancer cells, triggering their death. The engineered virus displayed an enhanced ability to debulk a PDA-derived tumour in xenograft mouse model. Our results highlight the possibility of selecting an IAV strain from the diverse natural avian reservoir on the basis of its inherent oncolytic potency in specific PDA subclasses and, through engineering, improve its safety, selectivity and debulking activity for cancer treatment.

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Section: The Immunostimulatory Activity Of H7n3 Ns1-77 Virus In Infecmentioning

confidence: 99%

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

Pizzuto

Silic-Benussi

Ciminale

et al. 2016

Journal of General Virology

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“…Currently, there are 600 citations that support the use of NDV in cancer therapy. Zamarin and Palese (2012) have published a very thorough and useful review of this literature.…”

Section: Viral Infection For Cancer Therapymentioning

confidence: 99%

“…Thus, inducing cell death by reducing the level and functionality of Hsps in cancer cells is an attractive strategy for cancer therapy (Galluzzi et al 2006;Jego et al 2010). Zamarin and Palese (2012) noted that virulence of NDV strains in birds correlates directly with their oncolytic properties. We suggest that there is also a direct correlation between the ability of virulent strains to inhibit host protein synthesis-including cellular stress protein synthesis-and the oncolytic properties of NDV.…”

Section: Viral Infection For Cancer Therapymentioning

confidence: 99%

Loss of stress response as a consequence of viral infection: implications for disease and therapy

Hooper

Hightower

Hooper

2012

Cell Stress and Chaperones

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“…The inherent viral oncolytic properties are believed to be derived from defective IFN signaling pathways in tumor cells. 3,5,8 The development of reverse genetics technology for NDV enable us to modify the NDV genome as well as introduce foreign sequences to refine the antitumor activity. [9][10][11][12][13] Previous studies in our laboratory showed that recombinant NDVs (rNDVs) expressing Trail, interleukin (IL) 15, and IL-2 are promising antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

Ren

Tian

Liu

et al. 2016

Technol Cancer Res Treat

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Interleukins as immunomodulators are promising therapeutic agents for cancer therapy. Previous studies showed that there was an improved antitumor immunity in tumor-bearing mice using recombinant Newcastle disease virus carrying for interleukin-2. Interleukin-12 is a promising antitumor cytokine too. So we investigated and compared the antitumor effect of genetically engineered Newcastle disease virus strains expressing both interleukin-12 and/or interleukin-2 (rClone30-interleukin-2, rClone30-interleukin-12, and rClone30-interleukin-12-interleukin-2). In vitro studies showed that rClone30s could efficiently infect tumor cells and express interleukin-12 and/or interleukin-2. 3-(4,5-Dimethylthiazol-2-y)-2,5-diphenyl-tetrazolium bromide results showed rClone30s possessed strong cytotoxic activities against multiple tumor cell lines (U251, HepG2, A549, and Hela). Animal studies showed that rClone30-interleukin-12-interleukin-2 was more effective in inhibition of murine hepatoma carcinoma tumors, with the mean tumor volume (day 14) of 141.70 mm 3 comparing 165.67 mm 3 of rClone30-interleukin-12 group, 210.47 mm 3 of rClone30-interleukin-2 group, 574.70 mm 3 of rClone30 group, and 1206.83 mm 3 of phosphate-buffered saline group. Moreover, the rClone30-interleukin-12-interleukin-2 treated mice secreted more interferon g (333.518 pg/mL) and its downstream cytokine interferon-g induced protein 10 (16.006 pg/mL) in tumor than the rClone30-interleukin-12 group (interferon g: 257.548 pg/mL; interferon-g induced protein 10: 13.601 pg/mL), rClone30-interleukin2 group (interferon g: 124.601 pg/mL; interferon-g induced protein 10: 9.779 pg/mL), or rClone30 group (interferon g: 48.630 pg/mL; interferon-g induced protein 10:1.650 pg/mL). For the survival study, rClone30-interleukin12-interleukin2 increased the survival rate (12 of 16) of the tumor-bearing mice versus 11 of 16 in rClone30-interleukin-12 group, 10 of 16 in rClone30-interleukin-2 group, 7 of 16 in Clone30 group, and 0/16 in phosphate-buffered saline group, respectively. To determine whether the mice treated with recombinant virus developed protective immune response, the mice were rechallenged with the same tumor cells. The results showed that viral-treated mice were significantly protected from rechallenge. These results suggest that expressing both interleukin-2 and/or interleukin-12 could be ideal approaches to enhance the antitumor ability of Newcastle disease virus, and rClone30-interleukin-12-interleukin-2 is slightly superior over rClone30-interleukin-12 and rClone30-interleukin-2 alone.

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Oncolytic Newcastle Disease Virus for Cancer Therapy: Old Challenges and New Directions

Cited by 206 publications

References 168 publications

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

Loss of stress response as a consequence of viral infection: implications for disease and therapy

Recombinant Newcastle Disease Virus Encoding IL-12 and/or IL-2 as Potential Candidate for Hepatoma Carcinoma Therapy

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