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Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68

Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC)...

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Autores principales: Gentschev, Ivaylo, Müller, Meike, Adelfinger, Marion, Weibel, Stephanie, Grummt, Friedrich, Zimmermann, Martina, Bitzer, Michael, Heisig, Martin, Zhang, Qian, Yu, Yong A., Chen, Nanhai G., Stritzker, Jochen, Lauer, Ulrich M., Szalay, Aladar A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133637/
https://www.ncbi.nlm.nih.gov/pubmed/21779374
http://dx.doi.org/10.1371/journal.pone.0022069
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author Gentschev, Ivaylo
Müller, Meike
Adelfinger, Marion
Weibel, Stephanie
Grummt, Friedrich
Zimmermann, Martina
Bitzer, Michael
Heisig, Martin
Zhang, Qian
Yu, Yong A.
Chen, Nanhai G.
Stritzker, Jochen
Lauer, Ulrich M.
Szalay, Aladar A.
author_facet Gentschev, Ivaylo
Müller, Meike
Adelfinger, Marion
Weibel, Stephanie
Grummt, Friedrich
Zimmermann, Martina
Bitzer, Michael
Heisig, Martin
Zhang, Qian
Yu, Yong A.
Chen, Nanhai G.
Stritzker, Jochen
Lauer, Ulrich M.
Szalay, Aladar A.
author_sort Gentschev, Ivaylo
collection PubMed
description Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.
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spelling pubmed-31336372011-07-21 Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68 Gentschev, Ivaylo Müller, Meike Adelfinger, Marion Weibel, Stephanie Grummt, Friedrich Zimmermann, Martina Bitzer, Michael Heisig, Martin Zhang, Qian Yu, Yong A. Chen, Nanhai G. Stritzker, Jochen Lauer, Ulrich M. Szalay, Aladar A. PLoS One Research Article Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man. Public Library of Science 2011-07-11 /pmc/articles/PMC3133637/ /pubmed/21779374 http://dx.doi.org/10.1371/journal.pone.0022069 Text en Gentschev et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gentschev, Ivaylo
Müller, Meike
Adelfinger, Marion
Weibel, Stephanie
Grummt, Friedrich
Zimmermann, Martina
Bitzer, Michael
Heisig, Martin
Zhang, Qian
Yu, Yong A.
Chen, Nanhai G.
Stritzker, Jochen
Lauer, Ulrich M.
Szalay, Aladar A.
Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title_full Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title_fullStr Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title_full_unstemmed Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title_short Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
title_sort efficient colonization and therapy of human hepatocellular carcinoma (hcc) using the oncolytic vaccinia virus strain glv-1h68
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133637/
https://www.ncbi.nlm.nih.gov/pubmed/21779374
http://dx.doi.org/10.1371/journal.pone.0022069
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