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Prophylactic anti-tumor immuntiy against a murine fibrosarcoma triggered by the Salmonella type III secretion system.
Microbes Infect. 8, 2539-2546 (2006)
The potential of an attenuated Salmonella enterica serovar Typhimurium strain as a prophylactic anti-tumor vaccine against the murine fibrosarcoma WEHI 164 was evaluated. Tumor cells were transfected with the DNA sequence encoding the MHC class I-restricted peptide p60(217-225) from Listeria monocytogenes. BALB/c mice received a single orogastric immunization with Salmonella that translocates a chimeric p60 protein via its type III secretion system. Mice were subsequently challenged subcutaneously with p60(217-225)-expressing WEHI cells. In vivo protection studies revealed that 80% of these mice remained free of the fibrosarcoma after challenge, whereas all animals of the non-vaccinated control group did develop tumor growth. In further experiments, the distribution of tetramer-positive p60(217-225)-specific effector and memory CD8 T cells after Salmonella-based immunization and tumor application was analyzed. Costaining with CD62L and CD127 revealed a predominance of p60-specific central memory and effector memory CD8 T cells in spleens, whereas in blood samples the majority of p60-specific lymphocytes belonged to effector and effector memory CD8 T cell subsets. This is the first report demonstrating that a bacterial type III secretion system can be used for heterologous antigen delivery to induce cytotoxic effector and memory CD8 T cell responses resulting in an efficient prevention of tumor growth.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Salmonella enterica serovar Typhimurium; Type III secretion system; tumor vaccine; CD8 T cell; memory T cell
ISSN (print) / ISBN
1286-4579
e-ISSN
1769-714X
Journal
Microbes and Infection
Quellenangaben
Volume: 8,
Issue: 9-10,
Pages: 2539-2546
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Antigen-specific Immunotherapy (VIRO-KVA)