CD8 T-Cell Induction against Vascular Endothelial Growth Factor Receptor 2 by Salmonella for Vaccination Purposes against a Murine Melanoma

  • Jellbauer S
  • Panthel K
  • Hetrodt J
 et al. 
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The Salmonella type III secretion system (T3SS) efficiently translocates heterologous proteins into the cytosol of eukaryotic cells. This leads to an antigen-specific CD8 T-cell induction in mice orally immunized with recombinant Salmonella. Recently, we have used Salmonella's T3SS as a prophylactic and therapeutic intervention against a murine fibrosarcoma. In this study, we constructed a recombinant Salmonella strain translocating the immunogenic H-2D(b)-specific CD8 T-cell epitope VILTNPISM (KDR2) from the murine vascular endothelial growth factor receptor 2 (VEGFR2). VEGFR2 is a member of the tyrosine protein kinase family and is upregulated on proliferating endothelial cells of the tumor vasculature. After single orogastric vaccination, we detected significant numbers of KDR2-tetramer-positive CD8 T cells in the spleens of immunized mice. The efficacy of these cytotoxic T cells was evaluated in a prophylactic setting to protect mice from challenges with B16F10 melanoma cells in a flank tumor model, and to reduce dissemination of spontaneous pulmonary melanoma metastases. Vaccinated mice revealed a reduction of angiogenesis by 62% in the solid tumor and consequently a significant decrease of tumor growth as compared to non-immunized mice. Moreover, in the lung metastasis model, immunization with recombinant Salmonella resulted in a reduction of the metastatic melanoma burden by approximately 60%.

Author-supplied keywords

  • angiogenesis
  • antigen delivery
  • bacterial-infection
  • host-cells
  • iii secretion system
  • immunotherapy
  • memory cells
  • selective expression
  • stem-like cells
  • tumor-growth

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  • Stefan Jellbauer

  • Klaus Panthel

  • Justin H Hetrodt

  • Holger Ruessmann

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