CD8+ T cells induce apoptosis of cancer cells, making them an attractive therapy. Vaccination generating a robust memory population of CD8+ T cells may provide protection against cancer. We investigated the generation of murine memory CD8+ T cells using a sustained antigen release vaccine vehicle (chitosan gel; Gel+OVA) containing a model antigen, ovalbumin, or conventional dendritic cell vaccination (DC+OVA) using the same protein antigen. The aims of this work were to evaluate the efficacy of Gel+OVA in generating memory CD8+ T cells at peripheral and gut associated lymphoid sites; and to determine whether this vaccination provided protection in murine tumour challenge models.
Mice were euthanised at memory time points following subcutaneous vaccination and cell populations were phenotypically assessed in peripheral and gut-associated lymphoid tissues using flow cytometry. Following vaccination with Gel+OVA, CD8+ T cell memory populations specific for ovalbumin protein were detected in both peripheral and gut-associated lymphoid organs. A subcutaneous melanoma model and an orthotopic colorectal cancer model were used to assess the protective capacity of Gel+OVA vaccination at peripheral and gut sites. Vaccination with Gel+OVA or DC+OVA increased survival of mice following subcutaneous tumour challenge compared to unvaccinated controls. Only vaccination with Gel+OVA gave decreased tumour burden compared to unvaccinated or DC+OVA-vaccinated mice in the colorectal cancer challenge model.
These results indicate that subcutaneous vaccination with Gel+OVA generates a population of functional CD8+ memory T cells in peripheral and gut-associated lymphoid tissue able to protect against tumour challenge. Vaccination with chitosan gel may be valuable in anti-cancer treatment at both peripheral and mucosal sites.