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Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice

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  • Zhenyu Zhong

    (Stritch School of Medicine, Loyola University Chicago
    Present address: Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093, USA)

  • Yougang Zhai

    (Stritch School of Medicine, Loyola University Chicago)

  • Ping Bu

    (Stritch School of Medicine, Loyola University Chicago
    Research Service, Edward Hines, Jr. VA Hospital)

  • Shivanee Shah

    (Stritch School of Medicine, Loyola University Chicago)

  • Liang Qiao

    (Stritch School of Medicine, Loyola University Chicago
    Biotherapy Center, The First Affiliated Hospital of Zhengzhou University
    Institute of Precision Medicine, Jining Medical University)

Abstract

Inducing tumour-specific adaptive immunity, such as cytotoxic T lymphocyte (CTL) response, can result in promising antitumour effect against several human malignancies, especially in combination with immune checkpoint blockade strategies. However, little is known whether activation of innate immunity can lead to direct tumoricidal effect. Here, we develop a papilloma pseudovirus-based oral immunotherapeutic approach that shows strong tumoricidal effects in the gut, resulting in an almost tripled lifespan of ApcMin/+ mice (an animal model of human intestinal tumorigenesis). Mechanistically, these pseudoviruses activate the NLRP3 and AIM2 inflammasomes, leading to caspase-1-mediated tumour regression that is dependent on neither cytotoxic T lymphocytes nor humoral immune response. Blocking caspase-1 activation abrogated the therapeutic effects of the pseudoviruses. Thus, targeting innate immune sensors in tumours by the pseudoviruses might represent a strategy to treat intestinal tumours.

Suggested Citation

  • Zhenyu Zhong & Yougang Zhai & Ping Bu & Shivanee Shah & Liang Qiao, 2017. "Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15004
    DOI: 10.1038/ncomms15004
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    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.

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