Monotherapy with a tumor-targeting mutant of S. typhimurium cures orthotopic metastatic mouse models of human prostate cancer

15641 Background: The evidence that bacteria have a therapeutic effect on tumors has been accumulating since the 19th century. In recent years, there has been renewed interest to develop bacteria that target necrotic tumor areas. However, this approach requires combination with cytotoxic chemotherapy for efficacy. Toward the goal of effective tumor-targeting bacteria as monotherapy, we have developed Salmonella typhimurium leu-arg auxotrophs (A1-R), which enable the bacteria to grow in viable as well as necrotic areas of tumors but not in normal tissue. Methods: In the current study, we determined the efficacy of A1-R on metastatic PC-3 human prostate tumors orthotopically implanted in nude mice. Ten of 20 orthotopically-implanted nude mice served as untreated controls and were followed until death. Ten mice were given the S. typhimurium A1-R weekly intravenously, beginning at 2 weeks when the tumor was first externally visible due to expression of green fluorescent protein. Survival time was compared to ...