Bioluminescence evaluation of efficacy of oncolytic treatment with Newcastle disease virus (NDV) in malignant pleural mesothelioma

Abstract

e14536 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from multipotent cells of the pleura. Chemotherapy and radiation have very limited therapeutic effects, and average survival time after diagnosis varies between 10 and 16 months. Immunotherapy, gene therapy (oncolytic viral therapy), and photodynamic therapy offer alternative treatment options, with promising results in animal studies. In the following study, the oncolytic efficacy of Newcastle disease virus (NDV(F3aa)-GFP) on MPM is tested and investigated by bioluminescence imaging. Methods: NDV(F3aa)-GFP was tested for viral cytotoxicity at different multiplicities of infection (MOI) against several mesothelioma cell lines in vitro by analyzing release of intracellular lactate dehydrogenase. For in vivo studies, MSTO 211H cells were transduced with firefly (Photinus pyralis) luciferase (FLuc)- encoding cDNAs (MSTO td 211H). Tumor-bearing animals (1e7 cells injected intrapleurally) were treated with either single or multiple doses of NDV(F3aa)-GFP (1e7 plaque-forming units) at different time points (days 1, 3, and 10) and followed by bioluminescence imaging. Results: Mesothelioma cell lines exhibited susceptibility to NDV lysis in the following order of sensitivity: MSTO 211H>MSTO td 211H>H-2452>VAMT>JMN. The cell lines H-2052, H-2373, and HMESO were not sensitive to viral treatment. In vivo studies with MSTO td 211H cells showed complete response to viral therapy in >75% of the animals, resulting in eradication of tumor detected by bioluminescence imaging at day 10 after treatment. Control animals were sacrificed after 23 days due to tumor burden, while >72% of the virally treated animals survived >50 days after tumor injection. No signs of toxicity were observed in the treatment group. In addition, multiple treatment showed a significantly better response compared with single treatment (p=0.005). Conclusions: NDV appears to be an efficient viral oncolytic agent in therapy of malignant pleural mesothelioma in a murine model, and warrants further investigation as a potential therapeutic agent. No significant financial relationships to disclose.