Targeted Therapy with aSalmonella TyphimuriumLeucine-Arginine Auxotroph Cures Orthotopic Human Breast Tumors in Nude Mice

Abstract

We report here a modified auxotrophic strain of Salmonella typhimurium that can target and cure breast tumors in orthotopic mouse models. We have previously reported development of a genetically modified strain of S. typhimurium, selected for prostate tumor targeting and therapy in vivo. The strain, termed S.

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

“…Preferential replication allows the bacteria to produce and deliver a variety of anticancer therapeutic agents at high concentrations directly within the tumor, while minimizing toxicity to normal tissues. 47,48 Attenuated S. typhimurium has been found to be safe in mice, pigs and monkeys when administered intravenously or by intra-abdominal routes. Thus, the combination of live attenuated bacteria as carriers for shRNAs and tumor growth inhibitors holds strong promise for tumor suppression.…”

Suppression of murine melanoma growth by a vaccine of attenuated Salmonella carrying heat shock protein 70 and Herpes simplex virus-thymidine kinase genes

“…In the meantime, the sub-cloning method was used to construct the control group plasmids pCMV-TK-IRES-EGFP and pCMV-mtHSP70-IRES-EGFP. (16). The plasmids of pCMV-mtHSP70-IRES-TK, pCMV-IRES-EGFP, pCMV-mtHSP70-IRES-EGFP and pCMV-TK-IRES-EGFP were transformed into Salmonella SL7207 (16) with an electroporator (Bio-Rad, USA).…”

Targeting Tumors with Salmonella Typhimurium - Potential for Therapy

“…Through the use of their flagella, Salmonella migrate towards the tumor, attracted by the high concentrations of nutrients available within the tumor microenvironment [20,21,22]. The metabolism of S. Typhimurium has been exploited to attenuate the strains used in cancer therapy, manipulating the bacteria so that they grow only at tumor sites.…”

“…Indeed, there are numerous compounds that can be delivered via bacteria to a tumor site including cytotoxic agents, green fluorescent protein for targeting and visualization of tumors, DNA for gene therapy, and small interfering RNAs (siRNA) to target expression of key proteins within tumors [11,22,26,27,28,29,30,31]. While these techniques have had varying levels of success in animal models, it is inferred that these practices when used in combination with the native toxicity of Salmonella may offer a fascinating alternative to traditional gene therapy approach.…”