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

Cancer Gene Therapy volume 15, pages 85–93 (2008)Cite this article

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.

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Acknowledgements

We thank G Dietrich for helpful discussions, Z Sokolovic and J Köhler for critical reading of the manuscript and J Reidl for the kind gift of V. cholerae DNA. This work was supported by grants from Aeterna Zentaris GmbH, Frankfurt (B Bergmann, CLRP Yone and I Gentschev) and from the Bavarian Research Cooperations Abayfor (Foringen; I Gentschev and UR Rapp).

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  1. U R Rapp and I Gentschev: UR Rapp and I Gentschev share senior authorship for this work.

Authors and Affiliations

  1. Institut für Medizinische Strahlenkunde und Zellforschung, University of Wuerzburg, Wuerzburg, Germany

    J Fensterle, B Bergmann, C L R P Yone, C Hotz, S R Meyer, U R Rapp & I Gentschev

  2. Æ,

    J Fensterle

  3. terna Zentaris GmbH, Weismüllerstr, Frankfurt, Germany

    J Fensterle

  4. Department of Microbiology, University of Wuerzburg, Wuerzburg, Germany

    B Bergmann, S Spreng & W Goebel

  5. Berna Biotech Ltd, Berne, Switzerland

    S Spreng

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  1. J Fensterle
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Correspondence to U R Rapp or I Gentschev.

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Fensterle, J., Bergmann, B., Yone, C. et al. Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B. Cancer Gene Ther 15, 85–93 (2008). https://doi.org/10.1038/sj.cgt.7701109

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