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Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pa...

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Autores principales: O’Leary, Michael P., Choi, Audrey H., Kim, Sang-In, Chaurasiya, Shyambabu, Lu, Jianming, Park, Anthony K., Woo, Yanghee, Warner, Susanne G., Fong, Yuman, Chen, Nanhai G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918769/
https://www.ncbi.nlm.nih.gov/pubmed/29699566
http://dx.doi.org/10.1186/s12967-018-1483-x
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author O’Leary, Michael P.
Choi, Audrey H.
Kim, Sang-In
Chaurasiya, Shyambabu
Lu, Jianming
Park, Anthony K.
Woo, Yanghee
Warner, Susanne G.
Fong, Yuman
Chen, Nanhai G.
author_facet O’Leary, Michael P.
Choi, Audrey H.
Kim, Sang-In
Chaurasiya, Shyambabu
Lu, Jianming
Park, Anthony K.
Woo, Yanghee
Warner, Susanne G.
Fong, Yuman
Chen, Nanhai G.
author_sort O’Leary, Michael P.
collection PubMed
description BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer. METHODS: After chimerization and high-throughput screening, CF33 was chosen from 100 new chimeric orthopoxvirus isolates for its ability to kill pancreatic cancer cells. In vitro cytotoxicity was assayed in six pancreatic cancer cell lines. In vivo efficacy and toxicity were evaluated in PANC-1 and MIA PaCa-2 xenograft models. RESULTS: CF33 caused rapid killing of six pancreatic cancer cells lines in vitro, releasing damage-associated molecular patterns, and regression of PANC-1 injected and non-injected distant xenografts in vivo after a single low intratumoral dose of 10(3) plaque-forming units. Using luciferase imaging, CF33 was noted to preferentially replicate in tumors which corresponds to the low viral titers found in solid organs. CONCLUSION: The low dose of CF33 required to treat pancreatic cancer in this preclinical study may ease the manufacturing and dosing challenges currently facing oncolytic viral therapy.
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spelling pubmed-59187692018-04-30 Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose O’Leary, Michael P. Choi, Audrey H. Kim, Sang-In Chaurasiya, Shyambabu Lu, Jianming Park, Anthony K. Woo, Yanghee Warner, Susanne G. Fong, Yuman Chen, Nanhai G. J Transl Med Research BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer. METHODS: After chimerization and high-throughput screening, CF33 was chosen from 100 new chimeric orthopoxvirus isolates for its ability to kill pancreatic cancer cells. In vitro cytotoxicity was assayed in six pancreatic cancer cell lines. In vivo efficacy and toxicity were evaluated in PANC-1 and MIA PaCa-2 xenograft models. RESULTS: CF33 caused rapid killing of six pancreatic cancer cells lines in vitro, releasing damage-associated molecular patterns, and regression of PANC-1 injected and non-injected distant xenografts in vivo after a single low intratumoral dose of 10(3) plaque-forming units. Using luciferase imaging, CF33 was noted to preferentially replicate in tumors which corresponds to the low viral titers found in solid organs. CONCLUSION: The low dose of CF33 required to treat pancreatic cancer in this preclinical study may ease the manufacturing and dosing challenges currently facing oncolytic viral therapy. BioMed Central 2018-04-26 /pmc/articles/PMC5918769/ /pubmed/29699566 http://dx.doi.org/10.1186/s12967-018-1483-x Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
O’Leary, Michael P.
Choi, Audrey H.
Kim, Sang-In
Chaurasiya, Shyambabu
Lu, Jianming
Park, Anthony K.
Woo, Yanghee
Warner, Susanne G.
Fong, Yuman
Chen, Nanhai G.
Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title_full Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title_fullStr Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title_full_unstemmed Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title_short Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
title_sort novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918769/
https://www.ncbi.nlm.nih.gov/pubmed/29699566
http://dx.doi.org/10.1186/s12967-018-1483-x
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