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

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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Oncolytic VSV-IFNβ-NIS is selectively destructive to tumors. Here, we present the IND enabling preclinical rodent studies in support of clinical testing of vesicular stomatitis virus (VSV) as a systemic therapy. Efficacy studies showed dose-dependent tumor regression in C57BL/KaLwRij mice bearing syngeneic 5TGM1 plasmacytomas after systemic VSV administration. In contrast, the virus was effective at all doses tested against human KAS6/1 xenografts in SCID mice. Intravenous administration of VSV-mIFNβ-NIS is well tolerated in C57BL/6 mice up to 5 × 1010 TCID50 (50% tissue culture infective dose)/kg with no neurovirulence, no cytokine storm, and no abnormalities in tissues. Dose-limiting toxicities included elevated transaminases, thrombocytopenia, and lymphopenia. Inactivated viral particles did not cause hepatic toxicity. Intravenously administered VSV was preferentially sequestered by macrophages in the spleen and liver. Quantitative RT-PCR analysis for total viral RNA on days 2, 7, 21, and 58 showed highest VSV RNA in day 2 samples; highest in spleen, liver, lung, lymph node, kidney, gonad, and bone marrow. No infectious virus was recovered from tissues at any time point. The no observable adverse event level and maximum tolerated dose of VSV-mIFNβ-NIS in C57BL/6 mice are 1010 TCID50/kg and 5 × 1010 TCID50/kg, respectively. Clinical translation of VSV-IFNβ-NIS is underway in companion dogs with cancer and in human patients with relapsed hematological malignancies and endometrial cancer.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalHuman Gene Therapy Clinical Development
Issue number3
StatePublished - Sep 1 2016

ASJC Scopus subject areas

  • Genetics(clinical)


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