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.
Highlights
Malignant mesothelioma (MM) is a very aggressive tumor developing from the mesothelium covering the body cavities
We recently demonstrated that the oncolytic adenovirus dl922-947 expressed antitumor effects in both MM cell lines and mouse xenografts and synergized with cisplatin [22], the drug currently used in MM
An appealing treatment for this tumor is oncolytic virotherapy, which has acquired an important role in cancer therapy, proving efficacy and safety in many clinical studies [16,17,18,19]
Summary
Malignant mesothelioma (MM) is a very aggressive tumor developing from the mesothelium covering the body cavities. The most common MM type affects the pleura surrounding the lungs. MMs are classified into three main histologic subtypes: epithelioid, sarcomatoid, and biphasic, which are characterized, respectively, by epithelial cells, spindle-shaped cells, or both cell types [1,2], and with sarcomatoid tumors determining the poorest outcome [2,3]. MM is mainly associated with asbestos exposure [4]. The use of asbestos has been banned in several countries, MM incidence is increasing due to both the long latency time between exposure and tumor occurrence and the persistence of environmental exposure [4]. Asbestos is still used in developing countries and the use of other asbestos-like fibers that can cause MM, such as erionite, is not strictly regulated [3]
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