Breast-tumor-targeted therapy with a Salmonella typhimurium LEU-ARG auxotroph

2171 We have previously developed an auxotrophic bacteria strain (A1) of Salmonella typhimurium that requires Leu and Arg that selectively targets the human PC-3 prostate in nude mouse models. The A1 strain selectively grew in the prostate tumors causing tumor regression. In sharp contrast, normal tissue is cleared of A1 bacteria even in nude mice with no apparent side effects. A1 is Leu/Arg-dependent but receives sufficient nutritional support from the neoplastic tissue. A1 grew throughout the tumor, including viable malignant tissue. This in contrast to anaerobic bacterial species and strains previously developed for cancer therapy where growth was confined to necrotic or hypoxic areas of the tumor. Growth in viable regions of the tumor may account, in part, for the A1’s unique antitumor efficacy. In the present report, in order to increase and broaden A1’s tumor-targeting capability, A1 sublines were re-isolated after infection of human colon tumors growing in nude mice. A tumor-isolated A1 subline (A1-1) had increased targeting for tumor cells in vivo as well as in vitro. Treatment with A1-1 resulted in effective tumor targeting and significant tumor shrinkage in mice with subcutaneous or orthotopic human MARY-X breast cancer xerographs. Survival of the treated animals was significantly prolonged. Forty percent of treated mice were cured completely and survived as long as control non-tumor-bearing mice. These results suggest that amino-acid auxotrophic S. typhimurium , which selectively infects and attacks viable tumor tissue, have potential for breast cancer therapy in the clinic.