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

BMC Immunol. 2016 Oct 18;17(1):39. doi: 10.1186/s12865-016-0178-4.

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.

Keywords: Caecum; Colon cancer; IFN-γ; T cells; Tumour; Vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cancer Vaccines / immunology*
  • Carcinogenesis
  • Cecum / immunology*
  • Cell Growth Processes
  • Chitosan / immunology*
  • Chitosan / therapeutic use
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Disease Models, Animal
  • Gels / administration & dosage
  • Humans
  • Immunity, Humoral
  • Immunologic Memory
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / trends
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Vaccination

Substances

  • Cancer Vaccines
  • Gels
  • Chitosan