IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15229-5.html
   My bibliography  Save this article

An engineered oncolytic virus expressing PD-L1 inhibitors activates tumor neoantigen-specific T cell responses

Author

Listed:
  • Guan Wang

    (Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California)

  • Xi Kang

    (Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California)

  • Katherine S. Chen

    (Fu Foundation School of Engineering and Applied Science, Columbia University)

  • Tiffany Jehng

    (Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California)

  • Lindsey Jones

    (Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California)

  • Jie Chen

    (Pomona Biotechnology Corp.)

  • Xue F. Huang

    (Pomona Biotechnology Corp.
    LifeSeq Limited Corp)

  • Si-Yi Chen

    (Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California)

Abstract

Oncolytic viruses offer an in situ vaccination approach to activate tumor-specific T cell responses. However, the upregulation of PD-L1 expression on tumor cells and immune cells leads to tumor resistance to oncolytic immunotherapy. In this study, we generate an engineered oncolytic virus that coexpresses a PD-L1 inhibitor and GM-CSF. We find that the oncolytic virus is able to secrete the PD-L1 inhibitor that systemically binds and inhibits PD-L1 on tumor cells and immune cells. Importantly, the intratumoral injection with the oncolytic virus overcomes PD-L1-mediated immunosuppression during both the priming and effector phases, provokes systemic T cell responses against dominant and subdominant neoantigen epitopes derived from mutations, and leads to an effective rejection of both virus-injected and distant tumors. In summary, this engineered oncolytic virus is able to activate tumor neoantigen-specific T cell responses, providing a potent, individual tumor-specific oncolytic immunotherapy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.

Suggested Citation

  • Guan Wang & Xi Kang & Katherine S. Chen & Tiffany Jehng & Lindsey Jones & Jie Chen & Xue F. Huang & Si-Yi Chen, 2020. "An engineered oncolytic virus expressing PD-L1 inhibitors activates tumor neoantigen-specific T cell responses," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15229-5
    DOI: 10.1038/s41467-020-15229-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15229-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-15229-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Shuo Wang & An Song & Jun Xie & Yuan-Yuan Wang & Wen-Da Wang & Meng-Jie Zhang & Zhi-Zhong Wu & Qi-Chao Yang & Hao Li & Junjie Zhang & Zhi-Jun Sun, 2024. "Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Jing Lin & Shihui Sun & Kui Zhao & Fei Gao & Renling Wang & Qi Li & Yanlong Zhou & Jing Zhang & Yue Li & Xinyue Wang & Le Du & Shuai Wang & Zi Li & Huijun Lu & Yungang Lan & Deguang Song & Wei Guo & Y, 2023. "Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15229-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.