Abstract 5398: A primer dose followed by low-bolus dose schedule for safe and efficacious bacterial tumor targeting with S. typhimurium A1-R

Abstract

Abstract We have previously developed a bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella typhimurium containing two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a relative safe treatment. The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg, and selected for high antitumor virulence, has been shown to be effective as monotherapy against human prostate, breast, pancreatic, and fibrosarcoma tumors that have been orthotopically implanted in nude mice. In the present study, we developed a strategy to maximize efficacy and minimize toxicity for bacterial tumor treatment. A small dose of S. typhimurium A1-R bacteria was first administered to tumor-bearing animals (the primer dose) as pre-treatment followed by a high dose (106 i.v.) 4 hours later. Compared with very high dose bacteria treatment (5 × 106 per mouse), the primer dose strategy had no observable side effects. The very high dose had toxicity in immunocompetent mice. The primer dose may induce cytokines in the mouse necessary for invasion of the tumor by the bacteria allowing a relatively small subsequent dose to be effective and safe. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5398. doi:10.1158/1538-7445.AM2011-5398