Lassa-VSV chimeric virus targets and destroys human and mouse ovarian cancer by direct oncolytic action and by initiating an anti-tumor response

Ovarian cancer is the third most common female cancer, with poor survival in later stages of metastatic spread. We test a chimeric virus consisting of genes from Lassa and vesicular stomatitis viruses, LASV-VSV; the native VSV glycoprotein is replaced by the Lassa glycoprotein, greatly reducing neur...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2021-03, Vol.555, p.44-55
Main Authors: van den Pol, A.N., Zhang, X., Lima, E., Pitruzzello, M., Albayrak, N., Alvero, A., Davis, J.N., Mor, G.
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Female
Humans
Lassa virus - immunology
Mice
Mice, Nude
Oncolytic Virotherapy - methods
Ovarian Neoplasms - therapy
Vesiculovirus - immunology
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Summary:Ovarian cancer is the third most common female cancer, with poor survival in later stages of metastatic spread. We test a chimeric virus consisting of genes from Lassa and vesicular stomatitis viruses, LASV-VSV; the native VSV glycoprotein is replaced by the Lassa glycoprotein, greatly reducing neurotropism. Human ovarian cancer cells in immunocompromised nude mice were lethal in controls. Chemotherapeutic paclitaxel and cisplatin showed modest cancer inhibition and survival extension. In contrast, a single intraperitoneal injection of LASV-VSV selectively infected and killed ovarian cancer cells, generating long-term survival. Mice with human ovarian cancer cells in brain showed rapid deterioration; LASV-VSV microinjection into brain blocked cancer growth, and generated long-term survival. Treatment of immunocompetent mice with infected mouse ovarian cancer cells blocked growth of non-infected ovarian cancer cells peritoneally and in brain. These results suggest LASV-VSV is a viable candidate for further study and may be of use in the treatment of ovarian cancer. •We understand that this section is optional and we would like to decline submitting any research highlights at this time.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2020.10.009