High Oncolytic Activity of a Double-Deleted Vaccinia Virus Copenhagen Strain against Malignant Pleural Mesothelioma

• Published in: Molecular therapy. Oncolytics Vol. 18; pp. 573 - 578
• Main Authors: Delaunay, Tiphaine, Nader, Joelle, Grard, Marion, Farine, Isabelle, Hedwig, Vera, Foloppe, Johann, Blondy, Thibaut, Violland, Mathilde, Pouliquen, Daniel, Grégoire, Marc, Boisgerault, Nicolas, Erbs, Philippe, Fonteneau, Jean-François
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 25-09-2020; American Society of Gene & Cell Therapy; Elsevier
• Subjects: oncolytic immunotherapy; oncolytic virus; Original; pleural mesothelioma; ribonucleotide reductase; thymidine kinase; vaccinia virus; ribonucleotide reductase; oncolytic immunotherapy; vaccinia virus; thymidine kinase; oncolytic virus; pleural mesothelioma
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2020.08.011

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.
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In this study, we show that VVTK-RR-/GFP, a Copenhagen vaccinia virus deleted of two virulence factors, replicates in and kills efficiently 22 human malignant pleural mesothelioma (MPM) cell lines. In mice bearing a human MPM xenograft, the VVTK-RR-/GFP increases its survival, highlighting the therapeutic potential of this virus against MPM.