CD8 T-cell induction against vascular endothelial growth factor receptor 2 by Salmonella for vaccination purposes against a murine melanoma.

Abstract

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%.

• Authors: Stefan Jellbauer, Klaus Panthel, Justin H Hetrodt, Holger Rüssmann
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e34214 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22511934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Recombinant Fusion Proteins
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Animals
• Cancer Vaccines
• Female
• Lung Neoplasms (prevention & control, secondary)
• Melanoma, Experimental (blood supply, prevention & control)
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (pathology)
• Recombinant Fusion Proteins (immunology)
• Salmonella typhimurium (genetics)
• T-Lymphocytes, Cytotoxic (physiology)
• Vaccination
• Vascular Endothelial Growth Factor Receptor-2 (immunology)