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Viruses. 2021 Dec 08;13(12). doi: 10.3390/v13122458.

The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.

Viruses

Iris Maria Forte, Paola Indovina, Serena Montagnaro, Aurora Costa, Carmelina Antonella Iannuzzi, Francesca Capone, Rosa Camerlingo, Anna Maria Malfitano, Francesca Pentimalli, Gianmarco Ferrara, Massimiliamo Quintiliani, Giuseppe Portella, Antonio Giordano, Roberto Ciarcia

Affiliations

  1. Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, 80131 Naples, Italy.
  2. Institute for High Performance Computing and Networking, National Research Council of Italy (ICAR-CNR), 80131 Naples, Italy.
  3. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
  4. Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", 80137 Naples, Italy.
  5. Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
  6. Experimental Pharmacology Unit-Laboratories of Naples and Mercogliano (AV), Istituto Nazionale per lo Studio e la Cura deiTumori "Fondazione G. Pascale", 80131 Naples, Italy.
  7. Dipartimento Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Naples, Italy.
  8. Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

PMID: 34960727 PMCID: PMC8703924 DOI: 10.3390/v13122458

Abstract

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.

Keywords: apoptosis; caprine herpesvirus 1 (CpHV-1); cisplatin; malignant mesothelioma (MM); oncolytic virus (OV); synergism

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