title: 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.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jellbauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Panthel
authors.forename: Justin H
authors.initials: JH
authors.lastname: Hetrodt
authors.forename: Holger
authors.initials: H
authors.lastname: Rüssmann
mesh_terms: D000818:Animals; D019496:Cancer Vaccines; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000098:blood supply / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014611:Vaccination; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2