Safety Studies in Tumor and Non-Tumor-Bearing Mice in Support of Clinical Trials Using Oncolytic VSV-IFNβ-NIS

Zhang, Lianwen; Steele, Michael B.; Jenks, Nathan J.; Grell, Jacquelyn A.; Suksanpaisan, Lukkana; Naik, Shruthi; Federspiel, Mark J.; Lacy, Martha Q.; Russell, Stephen J.; Peng, Kah Whye

doi:10.1089/humc.2016.061

Cited by 50 publications

(62 citation statements)

References 22 publications

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“…Using VSVs encoding type I and type III IFNs Several recent pre-clinical studies have shown that VSVIFNb and VSV-IFNb-NIS (additionally expresses the NIS to track virus spread) are oncoselective and safe in a variety of tumour and animal models [24,[27][28][29][30][31]. Although mice and rats continue to serve as the most commonly used animal models for VSV-based OV therapy, a recent study evaluated the safety of intravenously administered VSV-IFNb-NIS in purpose-bred beagle dogs.…”

Section: Improving Oncoselectivity and Safetymentioning

confidence: 99%

Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update

Felt

Grdzelishvili

2017

Journal of General Virology

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Oncolytic virus (OV) therapy is an anti-cancer approach that uses viruses that preferentially infect, replicate in and kill cancer cells. Vesicular stomatitis virus (VSV, a rhabdovirus) is an OV that is currently being tested in the USA in several phase I clinical trials against different malignancies. Several factors make VSV a promising OV: lack of pre-existing human immunity against VSV, a small and easy to manipulate genome, cytoplasmic replication without risk of host cell transformation, independence of cell cycle and rapid growth to high titres in a broad range of cell lines facilitating large-scale virus production. While significant advances have been made in VSV-based OV therapy, room for improvement remains. Here we review recent studies (published in the last 5 years) that address 'old' and 'new' challenges of VSV-based OV therapy. These studies focused on improving VSV safety, oncoselectivity and oncotoxicity; breaking resistance of some cancers to VSV; preventing premature clearance of VSV; and stimulating tumour-specific immunity. Many of these approaches were based on combining VSV with other therapeutics. This review also discusses another rhabdovirus closely related to VSV, Maraba virus, which is currently being tested in Canada in phase I/II clinical trials.

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Section: Improving Oncoselectivity and Safetymentioning

confidence: 99%

Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update

Felt

Grdzelishvili

2017

Journal of General Virology

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“…As clinical trials expand and more patients participate, more long-term or short-term adverse events will likely be reported and analyzed. In addition, with new discoveries of oncolytic virotherapies, increasing numbers of genetic modifications to oncolytic viruses, and additional recombinant viruses, microRNAs, and viral vectors found, the safety of oncolytic viruses in tumor immunotherapy will be further guaranteed (117,136,137).…”

Section: Methods To Improve the Biosafety Of Oncolytic Virotherapymentioning

confidence: 99%

Delivery and Biosafety of Oncolytic Virotherapy

et al. 2020

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In recent years, oncolytic virotherapy has emerged as a promising anticancer therapy. Oncolytic viruses destroy cancer cells, without damaging normal tissues, through virus self-replication and antitumor immunity responses, showing great potential for cancer treatment. However, the clinical guidelines for administering oncolytic virotherapy remain unclear. Delivery routes for oncolytic virotherapy to patients vary in existing studies, depending on the tumor sites and the objective of studies. Moreover, the biosafety of oncolytic virotherapy, including mainly uncontrolled adverse events and long-term complications, remains a serious concern that needs to be accurately measured. This review provides a comprehensive and detailed overview of the delivery and biosafety of oncolytic virotherapy.

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“…It is noteworthy that VSV was found to infect neutrophils and monocytes in the peripheral blood of mice [194]. Infective virus was also isolated from the spleen of treated animals and systemic inflammatory responses as well as hepatic toxicity were reported [195]. Fatal central nervous system toxicity was reported in mice treated with VSV and had meningeal MM deposits [193].…”

Section: Vesicular Stomatitis Virusmentioning

confidence: 99%