Original Article
Cancer Gene Therapy (2008) 15, 85–93; doi:10.1038/sj.cgt.7701109; published online 14 December 2007
Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B
J Fensterle1,2, B Bergmann1,3, C L R P Yone1, C Hotz1, S R Meyer1, S Spreng3,4, W Goebel3, U R Rapp1,5 and I Gentschev1,5
- 1Institut für Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, Wuerzburg, Germany
- 2Æterna Zentaris GmbH, Weismüllerstr, Frankfurt, Germany
- 3Department of Microbiology, University of Wuerzburg, Wuerzburg, Germany
- 4Berna Biotech Ltd, Berne, Switzerland
Correspondence: Dr I Gentschev and Dr UR Rapp, Institut für Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, D-97078 Wuerzburg, Germany. E-mails: ivaylo.gentschev@mail.uni-wuerzburg.de; rappur@mail.uni-wuerzburg.de
5UR Rapp and I Gentschev share senior authorship for this work.
Received 10 July 2007; Revised 5 October 2007; Accepted 6 November 2007; Published online 14 December 2007.
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.
Keywords:
bacterial cancer vaccines, prostate-specific antigen, cholera toxin subunit B, hemolysin (HlyA) secretion system (T1SS), cancer immunotherapy
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