High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a cancer of the pleura that lacks efficient treatment. Oncolytic immunotherapy using oncolytic vaccinia virus (VV) may represent an alternative therapeutic approach for the treatment of this malignancy. Here, we studied the oncolytic activity of VV thymidine k...
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doaj-6d67b79df4734bc992cb612a228e36e22020-11-25T01:38:26ZengElsevierMolecular Therapy: Oncolytics2372-77052020-09-0118573578High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural MesotheliomaTiphaine Delaunay0Joelle Nader1Marion Grard2Isabelle Farine3Vera Hedwig4Johann Foloppe5Thibaut Blondy6Mathilde Violland7Daniel Pouliquen8Marc Grégoire9Nicolas Boisgerault10Philippe Erbs11Jean-François Fonteneau12CRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceTransgene, 67400 Illkirch, FranceTransgene, 67400 Illkirch, FranceTransgene, 67400 Illkirch, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, FranceTransgene, 67400 Illkirch, FranceCRCINA, INSERM, Université d’Angers, Université de Nantes, 44007 Nantes, France; Labex IGO, Immunology Graft Oncology, 44007 Nantes, France; Corresponding author: Jean-François Fonteneau, CRCINA, INSERM UMR1232, Institut de Recherche en Santé de l’Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.Malignant pleural mesothelioma (MPM) is a cancer of the pleura that lacks efficient treatment. Oncolytic immunotherapy using oncolytic vaccinia virus (VV) may represent an alternative therapeutic approach for the treatment of this malignancy. Here, we studied the oncolytic activity of VV thymidine kinase (TK)-ribonucleotide reductase (RR)-/green fluorescent protein (GFP) against MPM. This virus is a VV from the Copenhagen strain that is deleted of two genes encoding the TK (J2R) and the RR (I4L) and that express the GFP. First, we show in vitro that VVTK-RR-/GFP efficiently infects and kills the twenty-two human MPM cell lines used in this study. We also show that the virus replicates in all eight tested MPM cell lines, however, with approximately a 10-fold difference in the amplification level from one cell line to another. Then, we studied the therapeutic efficiency of VVTK-RR-/GFP in non-obese diabetic (NOD) severe combined immunodeficient (SCID) mice that bear peritoneal human MPM tumors. One intraperitoneal infection of VVTK-RR-/GFP reduces the tumor burden and significantly increases mice survival compared to untreated animals. Thus, VVTK-RR- may be a promising oncolytic virus (OV) for the oncolytic immunotherapy of MPM.http://www.sciencedirect.com/science/article/pii/S2372770520301285oncolytic immunotherapyoncolytic virusvaccinia viruspleural mesotheliomathymidine kinaseribonucleotide reductase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tiphaine Delaunay Joelle Nader Marion Grard Isabelle Farine Vera Hedwig Johann Foloppe Thibaut Blondy Mathilde Violland Daniel Pouliquen Marc Grégoire Nicolas Boisgerault Philippe Erbs Jean-François Fonteneau |
spellingShingle |
Tiphaine Delaunay Joelle Nader Marion Grard Isabelle Farine Vera Hedwig Johann Foloppe Thibaut Blondy Mathilde Violland Daniel Pouliquen Marc Grégoire Nicolas Boisgerault Philippe Erbs Jean-François Fonteneau High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma Molecular Therapy: Oncolytics oncolytic immunotherapy oncolytic virus vaccinia virus pleural mesothelioma thymidine kinase ribonucleotide reductase |
author_facet |
Tiphaine Delaunay Joelle Nader Marion Grard Isabelle Farine Vera Hedwig Johann Foloppe Thibaut Blondy Mathilde Violland Daniel Pouliquen Marc Grégoire Nicolas Boisgerault Philippe Erbs Jean-François Fonteneau |
author_sort |
Tiphaine Delaunay |
title |
High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma |
title_short |
High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma |
title_full |
High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma |
title_fullStr |
High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma |
title_full_unstemmed |
High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma |
title_sort |
high oncolytic activity of a double-deleted vaccinia virus copenhagen strain against malignant pleural mesothelioma |
publisher |
Elsevier |
series |
Molecular Therapy: Oncolytics |
issn |
2372-7705 |
publishDate |
2020-09-01 |
description |
Malignant pleural mesothelioma (MPM) is a cancer of the pleura that lacks efficient treatment. Oncolytic immunotherapy using oncolytic vaccinia virus (VV) may represent an alternative therapeutic approach for the treatment of this malignancy. Here, we studied the oncolytic activity of VV thymidine kinase (TK)-ribonucleotide reductase (RR)-/green fluorescent protein (GFP) against MPM. This virus is a VV from the Copenhagen strain that is deleted of two genes encoding the TK (J2R) and the RR (I4L) and that express the GFP. First, we show in vitro that VVTK-RR-/GFP efficiently infects and kills the twenty-two human MPM cell lines used in this study. We also show that the virus replicates in all eight tested MPM cell lines, however, with approximately a 10-fold difference in the amplification level from one cell line to another. Then, we studied the therapeutic efficiency of VVTK-RR-/GFP in non-obese diabetic (NOD) severe combined immunodeficient (SCID) mice that bear peritoneal human MPM tumors. One intraperitoneal infection of VVTK-RR-/GFP reduces the tumor burden and significantly increases mice survival compared to untreated animals. Thus, VVTK-RR- may be a promising oncolytic virus (OV) for the oncolytic immunotherapy of MPM. |
topic |
oncolytic immunotherapy oncolytic virus vaccinia virus pleural mesothelioma thymidine kinase ribonucleotide reductase |
url |
http://www.sciencedirect.com/science/article/pii/S2372770520301285 |
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