Oncolytic virotherapy for human malignant mesothelioma: recent advances

Boisgerault, Nicolas; Achard, Catherine; Delaunay, Tiphaine; Cellerin, L.; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

doi:10.2147/ov.s66091

Cited by 7 publications

(6 citation statements)

References 70 publications

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“…Although OVs are potentially powerful therapeutic agents against cancer, they frequently prove to be more effective in combinatorial treatments and are often tested in combination with standard chemotherapeutic agents [19,22,55]. In the present study, we observed that CpHV-1 strongly synergized with cisplatin, and this agent combination exerted no toxic effect on mesothelial cells.…”

Section: Discussionsupporting

confidence: 47%

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

Forte

Indovina

Montagnaro

et al. 2021

Viruses

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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.

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Section: Discussionsupporting

confidence: 47%

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

Forte

Indovina

Montagnaro

et al. 2021

Viruses

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“…Therefore, investigating how to induce potent antitumor immune responses is essential for enhancing the therapeutic efficacy of virotherapy in patients. 3,45 Most of the viruses that are currently being tested in clinical trials were designed to acquire the capability to trigger immune responses. 4,5,41,42 To this end, understanding the mechanism underlying the blockade and regulation of systemic antitumor immunity is critical for the further improvement of oncolytic virotherapy.…”

Section: Discussionmentioning

confidence: 99%

Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression

et al. 2018

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Antitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. Although MVTT leads to regression of established mesothelioma dose-dependently, antitumor CTLs are rarely induced. Mechanistically, MVTT virotherapy generates C-X-C chemokines that recruit CXCR2-expressing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumor microenvironment, where they suppress dendritic cells (DCs) by producing IL-10 and halt CTL responses. During the virotherapy, however, depletion of PMN-MDSCs but not of monocytic (M)-MDSCs results in the induction of potent antitumor CTLs that not only eradicate established mesothelioma but also prevent the second tumor challenge. Our findings suggest that vaccinia virotherapy may combine strategies that prevent the chemotactic recruitment of PMN-MDSCs, block their suppression on DCs or deplete PMN-MDSCs in order to induce potent CTLs for tumor eradication.

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“…Notably CD46 is selectively expressed in malignant cells and not in inflammatory mesothelium, thus allowing for a highly specific delivery [ 138 ]. Overall combinations of oncolytic viruses with other types of cancer treatments results in synergistic effects [ 139 ]. Virotherapy, in combination with immunotherapy in particular, has shown promising results in MPM.…”

Section: Cutting-edge Molecularly Oriented Therapiesmentioning

confidence: 99%

The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

Lettieri

Bortolotto

Agustoni

et al. 2021

JCM

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Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and—in specific geographic regions—erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.

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Oncolytic virotherapy for human malignant mesothelioma: recent advances

Cited by 7 publications

References 70 publications

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

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

Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression

The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

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