In vivo bactofection: listeria can function as a DNA-cancer vaccine.
The development of an effective therapeutic vaccine to induce cancer-specific immunity remains an unsolved yet pressing priority requiring novel vaccine strategies. Here we have generated a series of vaccines in which bacteria deliver a plasmid encoding a tumor antigen under the control of a mammalian promoter in an attempt to induce an antitumor immune response. Utilizing a plasmid release mechanism involving the suicide of the carrier bacteria, we were able to engineer Listeria monocytogenes to induce antitumor immunity to a physiologically relevant tumor antigen, the cervical cancer oncoprotein E7. In a mouse model of cervical cancer, we were able to slow tumor growth and induce an effector CD8(+) T-cell response against the immunodominant epitope for E7. The CD8(+) T cells generated could both home to and penetrate the tumor. This is the first demonstration of in vivo efficacy of bactofection vectors in treating solid tumors. However, although this delivery system was more effective than administering plasmid alone, it was not as effective as L. monocytogenes engineered to deliver the E7 protein in impacting on established tumor growth.
Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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Souders
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T
Verch
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Paterson
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000032:analysis; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy / Q000821:virology; D010957:Plasmids; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D007371:Interferon-gamma