High oncolytic activity of a double deleted Vaccinia Virus Copenhagen strain against malignant pleural mesothelioma

Abstract 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 VVTK-RR-/GFP against MPM. This virus is a VV from the Copenhagen strain that is deleted of two genes encoding the thymidine kinase (J2R) and the ribonucleotide reductase (I4L) and that express the green fluorescent protein (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 differences in the amplification level from one cell line to another. Then we studied the therapeutic efficiency of VVTK-RR-/GFP in NOD 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 OV for the oncolytic immunotherapy of MPM.