Prostate cancer is the most common malignant tumor in men and is normally associated with increased serum levels of prostatespecific 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 þ T-cell responses resulting in an efficient prevention of tumor growth in mice.
Live, attenuated bacterial vaccines (LBV) are promising candidates for the induction of a broad-based immune response directed at recombinant heterologous antigens and the corresponding pathogen. LBVs allow vaccination through the mucosal surfaces and specific targeting of professional antigen-presenting cells located at the inductive sites of the immune system. A novel approach exploits attenuated intracellular bacteria as delivery vectors for eukaryotic antigen-expression plasmids (so-called DNA vaccines). Candidate carrier bacteria include attenuated strains of Gram-positive and Gram-negative bacteria. These bacteria have been shown to deliver DNA vaccines to human cells in vitro and have also proven their in vivo efficacy in several experimental animal models of infectious diseases and different cancers. The clinical assessment of the safety, immunogenicity and efficacy of these candidate strains will be the next challenging step towards live bacterial DNA vaccines.
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