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Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

BACKGROUND: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In...

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Autores principales: Gil, M, Bieniasz, M, Seshadri, M, Fisher, D, Ciesielski, M J, Chen, Y, Pandey, R K, Kozbor, D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242530/
https://www.ncbi.nlm.nih.gov/pubmed/21989183
http://dx.doi.org/10.1038/bjc.2011.429
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author Gil, M
Bieniasz, M
Seshadri, M
Fisher, D
Ciesielski, M J
Chen, Y
Pandey, R K
Kozbor, D
author_facet Gil, M
Bieniasz, M
Seshadri, M
Fisher, D
Ciesielski, M J
Chen, Y
Pandey, R K
Kozbor, D
author_sort Gil, M
collection PubMed
description BACKGROUND: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice. METHODS: The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay. RESULTS: Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue. CONCLUSION: These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV.
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spelling pubmed-32425302011-12-23 Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice Gil, M Bieniasz, M Seshadri, M Fisher, D Ciesielski, M J Chen, Y Pandey, R K Kozbor, D Br J Cancer Translational Therapeutics BACKGROUND: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice. METHODS: The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay. RESULTS: Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue. CONCLUSION: These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV. Nature Publishing Group 2011-11-08 2011-10-11 /pmc/articles/PMC3242530/ /pubmed/21989183 http://dx.doi.org/10.1038/bjc.2011.429 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Translational Therapeutics
Gil, M
Bieniasz, M
Seshadri, M
Fisher, D
Ciesielski, M J
Chen, Y
Pandey, R K
Kozbor, D
Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title_full Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title_fullStr Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title_full_unstemmed Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title_short Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
title_sort photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242530/
https://www.ncbi.nlm.nih.gov/pubmed/21989183
http://dx.doi.org/10.1038/bjc.2011.429
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