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

Zhenyu Zhong, Yougang Zhai, Ping Bu, Shivanee Shah, Liang Qiao

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 Apc Min/+ 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.

Original languageEnglish (US)
Article number15004
JournalNature communications
Volume8
DOIs
StatePublished - Apr 11 2017
Externally publishedYes

Fingerprint

Papilloma
mice
Tumors
tumors
Caspase 1
T-cells
lymphocytes
immunity
Cytotoxic T-Lymphocytes
Neoplasms
Chemical activation
activation
Inflammasomes
animal models
Adaptive Immunity
Therapeutic Uses
Humoral Immunity
Animals
Innate Immunity
Carcinogenesis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of Apc Min/+ mice. / Zhong, Zhenyu; Zhai, Yougang; Bu, Ping; Shah, Shivanee; Qiao, Liang.

In: Nature communications, Vol. 8, 15004, 11.04.2017.

Research output: Contribution to journalArticle

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