Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia.
Bottom Line: VSV-gp160G was further noted to be highly attenuated and did not replicate efficiently in or induce significant cell death of primary CD4(+) T cells.Importantly, VSV-gp160G effectively exerted potent oncolytic activity in patient-derived ATL transplanted into NSG mice and facilitated a significant survival benefit.This effect greatly reduced neurotoxic risk associated with VSV infection while still allowing VSV to effectively target ATL cells.
Affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.Show MeSH
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Mentions: To determine the biodistribution of both VSV-XN2 and VSV-gp160G in a naive NSG mouse model, 106 PFU of either virus were injected into the peritoneal cavity of individual mice on day 0, and then the mice (n = 4) were euthanized on days 1, 7, 14, and 21 postinfection. The presence of VSV in brain, lung, liver, and kidney was determined by plaque assay. Residual VSV-gp160G was only detectable in the kidney 1 day after inoculation. In contrast, VSV-XN2 grew to a considerable titer in the brain and kidneys of the mouse sacrificed on day 14, and the mouse exhibited symptoms consistent with VSV-mediated neurotoxicity (Fig. 7A).
Affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.