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Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2

Author

Listed:
  • Zuqiang Liu

    (University of Pittsburgh School of Medicine
    UPMC Hillman Cancer Center)

  • Yan Ge

    (University of Pittsburgh School of Medicine
    Soochow University)

  • Haiyan Wang

    (University of Pittsburgh School of Medicine
    Soochow University)

  • Congrong Ma

    (University of Pittsburgh School of Medicine
    UPMC Hillman Cancer Center)

  • Mathilde Feist

    (University of Pittsburgh School of Medicine
    Charité—Universitaetsmedizin Berlin)

  • Songguang Ju

    (Soochow University)

  • Z. Sheng Guo

    (University of Pittsburgh School of Medicine
    UPMC Hillman Cancer Center)

  • David L. Bartlett

    (University of Pittsburgh School of Medicine
    UPMC Hillman Cancer Center)

Abstract

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 microenvironment 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.

Suggested Citation

  • Zuqiang Liu & Yan Ge & Haiyan Wang & Congrong Ma & Mathilde Feist & Songguang Ju & Z. Sheng Guo & David L. Bartlett, 2018. "Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06954-z
    DOI: 10.1038/s41467-018-06954-z
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