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Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice

BACKGROUND: Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies. METHODS...

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Autores principales: Martikainen, Miika, Ruotsalainen, Janne, Tuomela, Johanna, Härkönen, Pirkko, Essand, Magnus, Heikkilä, Jari, Hinkkanen, Ari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520213/
https://www.ncbi.nlm.nih.gov/pubmed/28557974
http://dx.doi.org/10.1038/bjc.2017.151
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author Martikainen, Miika
Ruotsalainen, Janne
Tuomela, Johanna
Härkönen, Pirkko
Essand, Magnus
Heikkilä, Jari
Hinkkanen, Ari
author_facet Martikainen, Miika
Ruotsalainen, Janne
Tuomela, Johanna
Härkönen, Pirkko
Essand, Magnus
Heikkilä, Jari
Hinkkanen, Ari
author_sort Martikainen, Miika
collection PubMed
description BACKGROUND: Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies. METHODS: We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models. RESULTS: SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours. CONCLUSIONS: Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.
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spelling pubmed-55202132018-06-27 Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice Martikainen, Miika Ruotsalainen, Janne Tuomela, Johanna Härkönen, Pirkko Essand, Magnus Heikkilä, Jari Hinkkanen, Ari Br J Cancer Translational Therapeutics BACKGROUND: Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies. METHODS: We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models. RESULTS: SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours. CONCLUSIONS: Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials. Nature Publishing Group 2017-06-27 2017-05-30 /pmc/articles/PMC5520213/ /pubmed/28557974 http://dx.doi.org/10.1038/bjc.2017.151 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Translational Therapeutics
Martikainen, Miika
Ruotsalainen, Janne
Tuomela, Johanna
Härkönen, Pirkko
Essand, Magnus
Heikkilä, Jari
Hinkkanen, Ari
Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title_full Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title_fullStr Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title_full_unstemmed Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title_short Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
title_sort oncolytic alphavirus sfv-va7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520213/
https://www.ncbi.nlm.nih.gov/pubmed/28557974
http://dx.doi.org/10.1038/bjc.2017.151
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