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

Zhenyu Zhong,Yougang Zhai,Ping Bu,Shivanee Shah,L. Qiao

Published 2017 in Nature Communications

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. Innate immunity sensors are expressed by both tumour cells and tumour-associated myeloid cells. Here, the authors show that stimulation of the innate immunity response with pseudoviruses in a genetic mouse model of intestinal cancer triggers tumour regression via Caspase-1 activation.

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