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Cancer Gene Ther. 2012 Apr;19(4):238-46. doi: 10.1038/cgt.2011.81. Epub 2011 Dec 9.

Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity.

Author information

1
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.

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.

PMID:
22158521
DOI:
10.1038/cgt.2011.81
[Indexed for MEDLINE]

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