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Publication : Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of Apc<sup>Min/+</sup> mice.

First Author  Zhong Z Year  2017
Journal  Nat Commun Volume  8
Pages  15004 PubMed ID  28397782
Mgi Jnum  J:250403 Mgi Id  MGI:5920982
Doi  10.1038/ncomms15004 Citation  Zhong Z, et al. (2017) Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice. Nat Commun 8:15004
abstractText  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.
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