Bacterial infection occasionally has a marked
therapeutic effect on
malignancies, as noted as early as the 19th century. Recently, there have been attempts to develop
cancer treatment by using
tumor-targeting bacteria. These treatments were developed to deliver therapeutic molecules specifically to
tumors. Researchers used anaerobic microorganisms that preferentially grew in necrotic
tumor areas. However, the resulting
tumor killing was, at best, limited. We have developed a far more effective bacterial
cancer therapy by targeting viable
tumor tissue by using Salmonella typhimurium
leu-arg auxotrophs. Although these bacteria grow in viable as well as necrotic areas of
tumors, the nutritional auxo trophy severely restricts growth in normal tissue. In the current study, we measured the antitumor efficacy of the S. typhimurium A1-R mutant, which is auxotrophic for
leu-arg and has increased antitumor virulence selected by
tumor passage. A1-R was used to treat metastatic PC-3 human prostate
tumors that had been orthotopically implanted in nude mice. GFP was used to image
tumor and metastatic growth. Of the 10 mice with the PC-3
tumors that were injected weekly with S. typhimurium A1-R, 7 were alive and well at the time the last untreated mouse died. Four A1-R-treated mice remain alive and well 6 months after implantation. Ten additional nontumor-bearing mice were injected weekly to determine the toxicity of S. typhimurium A1-R. No toxic effects were observed. The approach described here, where bacterial monotherapy effectively treats metastatic prostate
tumors, is a significant improvement over previous bacterial
tumor-
therapy strategies that require combination with toxic
chemotherapy.