Chitosan gel vaccine protects against tumour growth in an intracaecal mouse model of cancer by modulating systemic immune responses

Abstract

Background: Vaccination generating a robust memory population of CD8+ T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. Methods: We used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention. We investigated the generation of murine memory CD8+ T cells using a sustained antigen release vaccine vehicle (chitosan gel; Gel+OVA) containing the model antigen ovalbumin, chitosan gel alone (Gel) or conventional dendritic cell vaccination (DC+OVA) using the same protein antigen. Results: Following vaccination with Gel+OVA, CD8+ T cell memory populations specific for ovalbumin protein were detected. Only vaccination with Gel+OVA gave decreased tumour burden compared to unvaccinated or DC+OVA-vaccinated mice in the intracaecal cancer challenge model. Conclusion: These results indicate that subcutaneous vaccination with Gel+OVA generates a population of functional CD8+ memory T cells in lymphoid tissue able to protect against intracaecal tumour challenge. Vaccination with chitosan gel may be valuable in anti-cancer treatment at both peripheral and mucosal sites.