Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B

Cancer Gene Ther. 2008 Feb;15(2):85-93. doi: 10.1038/sj.cgt.7701109. Epub 2007 Dec 14.

Abstract

Prostate cancer is the most common malignant tumor in men and is normally associated with increased serum levels of prostate-specific antigen (PSA). Therefore, PSA is one potential target for a prostate cancer vaccine. In this study we analyzed the functionality of new bacterial PSA vaccines, expressed and secreted via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of Type I secretion systems (T1SS) using an attenuated Salmonella enterica serovar Typhimurium aroA strain as carrier. The data demonstrate that a bacterial live vaccine encompassing T1SS in combination with cholera toxin subunit B can be successfully used for delivery of PSA to induce cytotoxic CD8+ T-cell responses resulting in an efficient prevention of tumor growth in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cholera Toxin / genetics
  • Cholera Toxin / immunology
  • Cholera Toxin / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Female
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Humans
  • Immunotherapy, Active*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / immunology
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / prevention & control*
  • Salmonella Vaccines / genetics
  • Salmonella Vaccines / immunology
  • Salmonella Vaccines / therapeutic use*
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / immunology
  • Typhoid-Paratyphoid Vaccines / genetics
  • Typhoid-Paratyphoid Vaccines / immunology
  • Typhoid-Paratyphoid Vaccines / therapeutic use*
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Cancer Vaccines
  • Escherichia coli Proteins
  • Hemolysin Proteins
  • Hlya protein, E coli
  • Salmonella Vaccines
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • aroA Salmonella vaccine
  • Cholera Toxin
  • Prostate-Specific Antigen