Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06954-z
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Funding
- NIH [P30CA047904]
- New Era Cap Company
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The complex immune tumour microenvironment requires an equally complex immunotherapy approach, especially when the cancer-immune set point is non-inflamed. Oncolytic viruses expressing immune activating cytokines might optimally modify the immune micro-environment and improve the antitumour effects. In this study, we have explored a variety of IL-2 constructs expressed by a tumour-selective oncolytic vaccinia virus, designed to maintain IL-2 in the tumour microenvironment to reduce systemic toxicity. An IL-2 construct combining a glycosylphosphatidylinositol (GPI) anchor with a rigid peptide linker leads to functional IL-2 expression on the tumour cell surface and in the tumour microenvironment. This virus construct effectively modifies the cancer-immune set point and treats a variety of murine tumour models with no toxic side effects. In combination with PD-1/PD-L1 blockade this virus cures most of the mice with a high tumour burden. This combination represents a treatment for cancers which are to date unresponsive to immunotherapy.
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