title: Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+mice.
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.
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois 60153, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois 60153, USA.
authors.forename: Yougang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Ophthalmology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois 60153, USA.|Research Service, Edward Hines, Jr. VA Hospital, Hines, Illinois 60141, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Bu
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois 60153, USA.
authors.forename: Shivanee
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois 60153, USA.|Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.|Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000276:immunology* / Q000628:therapy / Q000821:virology; D008136:Longevity / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D027383:Papillomaviridae / Q000276:immunology* / Q000502:physiology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D020170:Caspase 1