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

PLoS One. 2012;7(4):e34214. doi: 10.1371/journal.pone.0034214. Epub 2012 Apr 12.

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%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines*
  • Female
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / 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*

Substances

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