Prophylactic anti-tumor immunity against a murine fibrosarcoma triggered by the Salmonella type III secretion system

Microbes Infect. 2006 Aug;8(9-10):2539-46. doi: 10.1016/j.micinf.2006.07.004. Epub 2006 Aug 1.

Abstract

The potential of an attenuated Salmonella enterica serovar Typhimurium strain as a prophylactic anti-tumor vaccine against the murine fibrosarcoma WEHI 164 was evaluated. Tumor cells were transfected with the DNA sequence encoding the MHC class I-restricted peptide p60(217-225) from Listeria monocytogenes. BALB/c mice received a single orogastric immunization with Salmonella that translocates a chimeric p60 protein via its type III secretion system. Mice were subsequently challenged subcutaneously with p60(217-225)-expressing WEHI cells. In vivo protection studies revealed that 80% of these mice remained free of the fibrosarcoma after challenge, whereas all animals of the non-vaccinated control group did develop tumor growth. In further experiments, the distribution of tetramer-positive p60(217-225)-specific effector and memory CD8 T cells after Salmonella-based immunization and tumor application was analyzed. Costaining with CD62L and CD127 revealed a predominance of p60-specific central memory and effector memory CD8 T cells in spleens, whereas in blood samples the majority of p60-specific lymphocytes belonged to effector and effector memory CD8 T cell subsets. This is the first report demonstrating that a bacterial type III secretion system can be used for heterologous antigen delivery to induce cytotoxic effector and memory CD8 T cell responses resulting in an efficient prevention of tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Female
  • Fibrosarcoma / genetics
  • Fibrosarcoma / immunology*
  • Fibrosarcoma / prevention & control
  • Genes, MHC Class I
  • Mice
  • Salmonella typhi / metabolism*
  • Spleen / cytology
  • Spleen / immunology
  • Transfection

Substances

  • 60 kDa protein, Listeria monocytogenes
  • Bacterial Proteins
  • Cancer Vaccines