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Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models

The avian paramyxovirus, Newcastle disease virus (NDV), is a promising oncolytic agent that has been shown to be safe and effective in a variety of pre-clinical cancer models and human clinical trials. NDV preferentially replicates in tumor cells due to signaling defects in apoptotic and antiviral p...

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Autores principales: McAusland, Thomas M., van Vloten, Jacob P., Santry, Lisa A., Guilleman, Matthew M., Rghei, Amira D., Ferreira, Edgar M., Ingrao, Joelle C., Arulanandam, Rozanne, Major, Pierre P., Susta, Leonardo, Karimi, Khalil, Diallo, Jean-Simon, Bridle, Byram W., Wootton, Sarah K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868934/
https://www.ncbi.nlm.nih.gov/pubmed/33614913
http://dx.doi.org/10.1016/j.omto.2021.01.009
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author McAusland, Thomas M.
van Vloten, Jacob P.
Santry, Lisa A.
Guilleman, Matthew M.
Rghei, Amira D.
Ferreira, Edgar M.
Ingrao, Joelle C.
Arulanandam, Rozanne
Major, Pierre P.
Susta, Leonardo
Karimi, Khalil
Diallo, Jean-Simon
Bridle, Byram W.
Wootton, Sarah K.
author_facet McAusland, Thomas M.
van Vloten, Jacob P.
Santry, Lisa A.
Guilleman, Matthew M.
Rghei, Amira D.
Ferreira, Edgar M.
Ingrao, Joelle C.
Arulanandam, Rozanne
Major, Pierre P.
Susta, Leonardo
Karimi, Khalil
Diallo, Jean-Simon
Bridle, Byram W.
Wootton, Sarah K.
author_sort McAusland, Thomas M.
collection PubMed
description The avian paramyxovirus, Newcastle disease virus (NDV), is a promising oncolytic agent that has been shown to be safe and effective in a variety of pre-clinical cancer models and human clinical trials. NDV preferentially replicates in tumor cells due to signaling defects in apoptotic and antiviral pathways acquired during the transformation process and is a potent immunostimulatory agent. However, when used as a monotherapy NDV lacks the ability to consistently generate durable remissions. Here we investigate the use of viral sensitizer-mediated combination therapy to enhance the anti-neoplastic efficacy of NDV. Intratumoral injection of vanadyl sulfate, a pan-inhibitor of protein tyrosine phosphatases, in combination with NDV significantly increased the number and activation status of natural killer (NK) cells in the tumor microenvironment, concomitant with increased expression of interferon-β, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, leading to rapid tumor regression and long-term cures in mice bearing syngeneic B16-F10 melanomas. The anti-tumor efficacy of this combination therapy was abrogated when NK cells were depleted and when interferon-β expression was transiently suppressed. Tumor-specific CD8(+) T cell responses were not detected, nor were mice whose tumors regressed protected from re-challenge. This suggested efficacy of the combination therapy predominantly relied on the innate immune system. Importantly, efficacy was not limited to melanoma; it was also demonstrated in a murine prostate cancer model. Taken together, these results suggest that combining NDV with vanadyl sulfate potentiates an innate immune response that can potentiate rapid clearance of tumors, with type I interferon signaling and NK cells being important mechanisms of action.
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spelling pubmed-78689342021-02-19 Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models McAusland, Thomas M. van Vloten, Jacob P. Santry, Lisa A. Guilleman, Matthew M. Rghei, Amira D. Ferreira, Edgar M. Ingrao, Joelle C. Arulanandam, Rozanne Major, Pierre P. Susta, Leonardo Karimi, Khalil Diallo, Jean-Simon Bridle, Byram W. Wootton, Sarah K. Mol Ther Oncolytics Original Article The avian paramyxovirus, Newcastle disease virus (NDV), is a promising oncolytic agent that has been shown to be safe and effective in a variety of pre-clinical cancer models and human clinical trials. NDV preferentially replicates in tumor cells due to signaling defects in apoptotic and antiviral pathways acquired during the transformation process and is a potent immunostimulatory agent. However, when used as a monotherapy NDV lacks the ability to consistently generate durable remissions. Here we investigate the use of viral sensitizer-mediated combination therapy to enhance the anti-neoplastic efficacy of NDV. Intratumoral injection of vanadyl sulfate, a pan-inhibitor of protein tyrosine phosphatases, in combination with NDV significantly increased the number and activation status of natural killer (NK) cells in the tumor microenvironment, concomitant with increased expression of interferon-β, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, leading to rapid tumor regression and long-term cures in mice bearing syngeneic B16-F10 melanomas. The anti-tumor efficacy of this combination therapy was abrogated when NK cells were depleted and when interferon-β expression was transiently suppressed. Tumor-specific CD8(+) T cell responses were not detected, nor were mice whose tumors regressed protected from re-challenge. This suggested efficacy of the combination therapy predominantly relied on the innate immune system. Importantly, efficacy was not limited to melanoma; it was also demonstrated in a murine prostate cancer model. Taken together, these results suggest that combining NDV with vanadyl sulfate potentiates an innate immune response that can potentiate rapid clearance of tumors, with type I interferon signaling and NK cells being important mechanisms of action. American Society of Gene & Cell Therapy 2021-01-21 /pmc/articles/PMC7868934/ /pubmed/33614913 http://dx.doi.org/10.1016/j.omto.2021.01.009 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
McAusland, Thomas M.
van Vloten, Jacob P.
Santry, Lisa A.
Guilleman, Matthew M.
Rghei, Amira D.
Ferreira, Edgar M.
Ingrao, Joelle C.
Arulanandam, Rozanne
Major, Pierre P.
Susta, Leonardo
Karimi, Khalil
Diallo, Jean-Simon
Bridle, Byram W.
Wootton, Sarah K.
Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title_full Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title_fullStr Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title_full_unstemmed Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title_short Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
title_sort combining vanadyl sulfate with newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868934/
https://www.ncbi.nlm.nih.gov/pubmed/33614913
http://dx.doi.org/10.1016/j.omto.2021.01.009
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