In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines

J Clin Invest. 2006 Jul;116(7):1946-54. doi: 10.1172/JCI28045. Epub 2006 Jun 22.


Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice resulted in the regression of established NY-ESO-1-expressing tumors. Intratumoral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1-specific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimurium type III secretion system is a promising novel strategy for cancer vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / immunology
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines*
  • Cell Line, Tumor
  • Epitopes
  • Female
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*


  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Epitopes
  • Membrane Proteins
  • Recombinant Proteins