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 evaluate the safety of VSV-gp160G in immunocompromised hosts, we performed preliminary toxicity assays using NSG (NOD/Shi-scid, IL-2Rγ-c-) mice. NSG mice are severely immunocompromised, lacking mature T cells, B cells, and functional NK cells. They are also deficient in cytokine signaling. All of which makes them both highly susceptible to VSV infection and excellent recipients for engraftment of human cells. NSG animals (n = 7) were inoculated intranasally with either 3 × 105 PFU of VSV-gp160G or with 1 × 103 or 3 × 105 PFU of VSV-XN2. We observed that NSG mice inoculated with VSV-XN2 at the higher dose succumbed rapidly to neurotoxicity, while the lower dose resulted in ca. 60% survival. In contrast, mice inoculated with VSV-gp160G did not experience any symptoms, and there were no mortalities (Fig. 6A).
Affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.