Mesothelioma is an infrequent malignancy of the parietal and visceral mesothelium, among which Malignant Pleural Mesothelioma (MPM) takes up for 90% of cases, as inhalation asbestos exposure is the main risk factor. Although with aggressive multimodality treatment of surgery, radiation, and/or chemotherapy, the median survival is just 1–2 years depending on stage and histology. Due to the limited effectiveness of common therapy for MPM, novel strategies for this difficult disease are severely needed. Nowadays, Oncolytic Viral (OV) therapy has emerged as a rapidly advancing field of immunotherapy studied in a broad spectrum of malignancies. Mesothelioma is an ideal candidate for exploring oncolysis, because it gives the frequently localized pattern of growth and pleural location offering access to direct intratumoral injection of virus. Based on the comprehensive OncoVirapy™ platform we have built, Creative Biolabs is capable of developing specific oncolytic virotherapy strategy for mesothelioma, as well as providing OV construction and validation services to customers all over the world.
The ideal OV therapy is depended on three basic principles: antitumor efficacy, tumor selectivity, as well as stimulation of the immune system. MPM offers an optimal model for the study of oncolytic virotherapy for many reasons. For example, its pleural location is accessible for direct IT injection, which is the preferred approach of administration for most viral platforms. Due to its characteristics, despite being an unusual malignancy, a board range of preclinical data with OVs in mesothelioma models is available. Currently, there are various OVs being studied for MPM, including Adenovirus, HSV Type 1, Vaccinia virus, Measles virus, Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Reovirus, and Sendai virus. To date, the majority of studies for OV therapy for MPM have been as monotherapy, necessary to determine viral activity, dosing, and safety in preclinical and early-phase human trials. Nevertheless, many researches have successfully combined virotherapy for mesothelioma with chemotherapy, surgery, and radiation.
Fig 1. The basic principles of oncolytic virotherapy. (Pease, D. F., 2017)
HSV-1 is a double-stranded DNA virus, and Recombinant HSV-1 has been studied in many malignancies, such as colorectal, pancreatic carcinoma and melanoma. The only FDA approved OV, T-VEC for melanoma, is a modified HSV-1. A preclinical study has tested three different replication-competent, oncolytic herpesviruses: G207, NV1020, and NV1066. These OVs are measured against 11 different MPM cell lines in vitro, and all of them were cytotoxic to each cell line, even at low multiplicities of infection. In addition, a replication-competent vaccinia virus GLV-1h68 has successfully replicated in and lysed multiple MPM cell lines in vitro. Then researchers established a murine model of MPM followed by intrapleural delivery of the virus which led to reduced tumor burden and improved survival.
With the rapid progress of novel therapeutic strategies in mesothelioma, oncolytic virus continues to hold promise as an effective treatment. Based on our advanced OncoVirapy™ platform, Creative Biolabs is confident in providing novel OVs and developing more efficient oncolytic virotherapy strategies for our customers.
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