Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium.
Salmonella typhimurium genetically modified at the purI and msbB genes to increase dependence on adenine and decrease stimulation of tumor necrosis factor-alpha production were injected intravenously into C57BL/6 mice bearing subcutaneous tumor or lung metastases. Decreased tumor growth and prolonged survival were seen in some, but not all of nine transplantable tumors. Salmonella increased in number in the tumor and reached levels 10,000 times higher than in the normal liver reservoir of these bacteria. Histologic studies revealed Salmonella growth in areas of the tumor although, in all cases, a viable rim of tumor survived and ultimately resulted in progressive tumor growth in all mice. These studies demonstrate that Salmonella can localize to transplantable murine tumors and partially inhibit tumor growth; however, additional modifications of the bacteria may be necessary if this approach is to develop into an effective treatment for patients with cancer.
Rosenberg
Steven A
SA
Surgery Branch and Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Spiess
Paul J
PJ
Kleiner
David E
DE
D000818:Animals; D007275:Injections, Intravenous; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D012486:Salmonella typhimurium / Q000276:immunology*