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 × 10(10) 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 10(10) TCID50/kg and 5 × 10(10) 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.