(c,d) The 14-week-old mice were orally immunized with VLP-hCEA. key component of gut mucosa, intestinal epithelial cells (IECs) absorb nutrients, provide a niche for commensal bacteria and prevent invasion of harmful pathogens1. However, when the biogenesis of Deoxycholic acid IECs is dysregulated, which often occurs as a result of the inherited genetic mutation, it can lead to the development of intestinal tumours. Conventional tumour vaccines aiming at Deoxycholic acid inducing tumour antigen-specific immunity have shown limited efficacy in the clinical trials that is most likely due to the immunosuppressive microenvironment in the tumours. Mucosal IECs and immune cells express a number of innate immune sensors, such as Toll-like receptors and Nod-like receptors (NLRs)2, for IL6R pathogen recognition. Activation of these immune sensors induces production of messengers (that is, chemokines/cytokines) that further recruit immune cells (for example, phagocytes, dendritic cells and adaptive immune cells) to join the battle against the invading pathogens1,3,4. In epithelial cell-derived tumours (for example, intestinal tumours), tumour cells and tumour-associated myeloid cells express Toll-like receptors/NLRs4,5. Expression of these receptors, in principle, offers ample opportunities to initiate an innate immune response, a critical prerequisite for inducing the adaptive immunities against tumours2. However, tumour-associated myeloid cells in the gut often produce immunosuppressive mediators that blunt the beneficial immune responses elicited upon vaccination6,7. It is therefore not clear whether intestinal tumour cells or tumour-associated myeloid Deoxycholic acid cells can be targeted to induce mucosal immunity, and whether such immunity has a positive or negative role on intestinal tumour progression. To address this question, we thought to induce both the innate and adaptive mucosal immunities in tumour-bearing animals and investigate whether and how such immunities may have an impact on tumour growth in the gut. We took advantage of the (multiple intestinal neoplasia) mice that have a mutation in the gene and develop intestinal adenomatous polyps, a type of benign tumour that are mainly in the small intestine8. These mice, which serve as a well-characterized animal model for human familial adenomatous polyposis, can develop more than 60 benign polyps in their entire intestines by 5 months of age, and some of these polyps can eventually progress to adenocarcinomas9,10. We used pseudoviruses from papillomaviruses, which belong to a group of small DNA nonlytic viruses Deoxycholic acid with skin- and mucosa-tropic properties11, as a tool to induce immune response against tumours in the mice. Papilloma pseudoviruses (PsVs) comprised a shell’ (also called virus-like particles (VLPs)) that is made of self-assembled Deoxycholic acid papillomavirus viral L1 protein and a nonviral plasmid that is packaged inside the VLP12,13. The binding and uptake of PsVs or VLPs depends on heparan sulfate proteoglycans with a special conformation14. Consistent with this notion, PsVs and VLPs were recently shown to be capable of pseudoinfecting’ tumour cells but not healthy epithelial and mesothelial tissues, because nontumour cells lack the presence of such specifically modified heparan sulfate proteoglycans on their plasma membrane15. Due to their unique tropisms, we reason that pseudoviruses can serve as ideal vehicles’ for delivering protein antigens, which are either presented by VLPs or encoded by an encapsulated plasmid, to mucosal tumour and/or lymphoid tissues16,17,18,19. Although pseudoviruses do not self-replicate, they retain the immunogenicity of a virus due to the presence of capsid and DNA that are able to activate innate immunity20,21,22. We hypothesize that, by infecting mucosal tumours and lymphoid tissues, PsVs would elicit antitumour innate and adaptive immunities to eradicate established tumours in the gut of mice. To test this hypothesis, we introduce a tumour-associated antigen (human carcinoembryonic antigen (hCEA)) into intestinal tumours of mice by crossing the mice with human CEA-transgenic (mice have roughly similar kinetics.