[HTML][HTML] Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the …

KB Stephenson, NG Barra, E Davies, AA Ashkar… - Cancer gene …, 2012 - nature.com
KB Stephenson, NG Barra, E Davies, AA Ashkar, BD Lichty
Cancer gene therapy, 2012nature.com
In this study, we sought to enhance the potency of an oncolytic virus, vesicular stomatitis
virus (VSV), by inserting a transgene encoding a highly secreted version of human
interleukin-15 (IL-15). IL-15 has shown promise as an immunotherapeutic cytokine, as it is
able to enhance both natural killer (NK) and T-cell responses, but it has not yet been tested
as a therapeutic transgene in the context of viral oncolysis. The transgene was modified to
ensure enhanced secretion of IL-15 from infected cells, leading to strong localized …
Abstract
In this study, we sought to enhance the potency of an oncolytic virus, vesicular stomatitis virus (VSV), by inserting a transgene encoding a highly secreted version of human interleukin-15 (IL-15). IL-15 has shown promise as an immunotherapeutic cytokine, as it is able to enhance both natural killer (NK) and T-cell responses, but it has not yet been tested as a therapeutic transgene in the context of viral oncolysis. The transgene was modified to ensure enhanced secretion of IL-15 from infected cells, leading to strong localized expression from infected CT-26 tumors in vivo. This localized expression in the tumor microenvironment led to a clear enhancement to anti-tumoral T-cell responses and enhanced survival, while additional IL-15 administration systemically failed to further enhance the therapy. Overall, the transient localized expression of IL-15 in the tumour by an oncolytic virus was able to induce stronger anti-tumoral immunity in a murine model of colon carcinoma.
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