Prophylactic anti-tumor immunity against a murine fibrosarcoma triggered by the Salmonella type III secretion system.
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.
Panthel
Klaus
K
Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 9a, 80336 Munich, Bavaria, Germany.
Meinel
Katrin M
KM
Sevil Domènech
Victòria E
VE
Geginat
Gernot
G
Linkemann
Kathrin
K
Busch
Dirk H
DH
Rüssmann
Holger
H
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D005805:Genes, MHC Class I; D051379:Mice; D012485:Salmonella typhi / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014162:Transfection
C078516:60 kDa protein, Listeria monocytogenes; D001426:Bacterial Proteins; D019496:Cancer Vaccines