Tumor antigen delivered by Salmonella III secretion protein fused with heat shock protein 70 induces protection and eradication against murine melanoma

Cancer Sci. 2010 Dec;101(12):2621-8. doi: 10.1111/j.1349-7006.2010.01722.x. Epub 2010 Sep 30.

Abstract

Attenuated Salmonella typhimurium possess the ability to stimulate innate immune responses and preferentially allocate within the solid tumor. These two main characteristics make attenuated Salmonella one of the most attractive vehicles for development of vaccine and also targeted cancer therapies. However, location of Salmonella prevents the process of antigen presentation. Salmonella Type III secretion system can be utilized to circumvent this problem because this system secretes the protein it encoded outside the cells. Heat shock protein 70 (Hsp70) is referred to as an "immunochaperone" for its capacity to elicit tumor-specific adaptive immune responses in the form of Hsp70-TAA (tumor associated antigen) complex. Hsp70 facilitates the cross-presentation of exogenous antigens through its receptor on antigen-presenting cells and therefore activates an antigen-specific cytotoxic T lymphocyte (CTL) response, which can directly contribute to potent anti-tumor immunity. Here, we designed a novel therapeutic vaccine utilizing the type III secretion system and Hsp70 to deliver and present the tumor-specific antigen. This live recombinant bacteria vaccine, when administrated orally, successfully broke the immune tolerance, induced a specific CTL response against tumor cells, and therefore revealed protective and therapeutic effects against generation and growth of B16F10 melanoma in C57BL/6J mice.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Bacterial Proteins / immunology
  • Bacterial Proteins / therapeutic use*
  • Bacterial Secretion Systems / immunology
  • Cancer Vaccines / immunology*
  • Cell Separation
  • Cross-Priming / immunology
  • Flow Cytometry
  • Genetic Vectors
  • HSP70 Heat-Shock Proteins / immunology
  • HSP70 Heat-Shock Proteins / therapeutic use*
  • Lymphocyte Activation / immunology
  • Male
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Membrane Proteins / immunology
  • Membrane Proteins / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use*
  • Salmonella typhimurium / immunology
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use

Substances

  • Antigens, Neoplasm
  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Cancer Vaccines
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • Peptide Fragments
  • SopE protein, Salmonella
  • Vaccines, Synthetic
  • peptide SVYDFFVWL