Tumor-seeking Salmonella amino acid auxotrophs.

A paradigm change in the treatment of cancer is urgently needed. Bacteria offer many advantages, including natural cytotoxity, motility, chemotaxis and a relative large genome to manipulate for tumor targeting. Salmonella, Clostridium, Bifodobacterium and Escherichia coli have been shown to control tumor growth and promote survival in animal models. We have developed an effective bacterial cancer therapy by engineering Salmonella typhimurium amino acid auxotrophs which grow in viable as well as necrotic areas of tumors, but not normal tissue. The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg, is tumor-seeking and has antitumor efficacy against the major types of cancer. The approach described here is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy.