Measles Virus Induces Oncolysis of Mesothelioma Cells and Allows Dendritic Cells to Cross-Prime Tumor-Specific CD8 Response

Abstract

Despite conventional medical and surgical treatments, malignant pleural mesothelioma (MPM) remains incurable. Oncovirotherapy (i.e., the use of replication-competent virus for cancer treatment) is currently explored in clinical trials. In this study, we investigated the antineoplastic potential of a new oncolytic viral agent, a live-attenuated measles virus (MV) strain derived from the Edmonston vaccine lineage (Schwarz strain). We evaluated both oncolytic activity and immunoadjuvant properties of the MV vaccine strain on mesothelioma tumor cells. Infectivity, syncytium formation, and cytolytic activity of MV were studied on a panel of mesothelioma cells derived from pleural effusions of MPM patients. We observed that MV infected preferentially MPM cell lines in comparison with nontransformed mesothelial cells, leading to an efficient killing of a significant fraction of tumor cells. A cytoreductive activity was also evidenced through formation of multinuclear cellular aggregates (syncytia). The susceptibility of MPM cell lines to measles infection was assessed by the analysis of cell surface expression of the MV vaccine receptor (CD46). We also evaluated whether MV infection of mesothelioma cells could elicit an autologous antitumor immune response. We showed that MV Schwarz strain induced apoptotic cell death of infected mesothelioma cells, which were efficiently phagocytosed by dendritic cells (DC). Loading of DCs with MV-infected MPM cells induced DC spontaneous maturation, as evidenced by the increased expression of MHC and costimulatory molecules along with the production of proinflammatory cytokines. Priming of autologous T cells by DCs loaded with MV-infected MPM cells led to a significant proliferation of tumor-specific CD8 T cells. Altogether, these data strongly support the potential of oncolytic MV as an efficient therapeutic agent for mesothelioma cancer. [Cancer Res 2008;68(12):4882-92]

Measles Virus Vaccine–Infected Tumor Cells Induce Tumor Antigen Cross-Presentation by Human Plasmacytoid Dendritic Cells

“…Indeed, measles virus vaccine infection of tumor cells may also be able to trigger the immune system to induce an antitumor immune response. We previously showed, in vitro, that mesothelioma cells killed by measles virus vaccine were able to produce danger signals, trigger the maturation of myeloid dendritic cells, and cross-present tumor antigens to CD8 þ T lymphocytes, whereas the same tumor cells killed by UV irradiation did not (7). Similar results were recently reported following lysis of melanoma tumor cells by measles virus vaccine (12).…”

“…Live-attenuated Schwarz-strain measles virus vaccine and recombinant measles virus vaccine-enhanced GFP (MVeGFP) were produced as previously described (7). Measles virus vaccine infection of tumor cells was conducted for 2 hours at 37 C with a multiplicity of infection (MOI) of 1 unless otherwise indicated.…”

Canine Distemper Virus Selectively Inhibits Apoptosis Progression in Infected Immune Cells

“…MeV infection results in apoptosis in Vero cells and human monocytic or promonocytic cell lines (10), as well as in primary cultured monocytes and dendritic cells (12). This capacity to induce apoptosis in infected cells and the resulting presentation of tumor antigens is increasingly exploited in oncolytic gene therapy approaches (13,21).…”

Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies

“…Significant evidences of preclinical activity have been obtained in MM in particular for measles virus (MV) [206,207]. MV-NIS is an attenuated MV expressing the human thyroidal sodium iodide symporter (NIS), which allows radiologic detection of the virus distribution and combination with radiometabolic therapy with iodine [206].…”