Biodistribution and genetic stability of the novel antitumor agent VNP20009, a genetically modified strain of Salmonella typhimurium

VNP20009 is a genetically modified strain of Salmonella typhimurium possess ing an excellent safety profile, including genetically stable attenuated vi rulence (a deletion in the purI gene), reduction of septic shock potential (a deletion in the msbB gene), and antibiotic susceptibility. VNP20009 is g enetically stable after multiple generations in vitro and in vivo. In mice, VNP20009 is rapidly cleared from the blood from a peak level of 1 x 10(4) cfu/mL to undetectable levels in 24 h. in tumor-bearing mice, VNP20009 accu mulates preferentially in tumors over livers at a ratio of 1000 : 1. In non human primates, VNP20009 was also rapidly cleared from the blood, from a pe ak level of 1.0 x 10(6) cfu/ml to undetectable levels in 24 h. VNP20009 was detected in the liver, spleen, and bone marrow of monkeys; the amount decr eased over time, and VNP20009 was cleared from all organs by day 41; no VNP 20009 could be detected in the urine or feces of the monkeys. VNP20009 is g enetically stable after many generations of growth (>140) both in vitro and in vivo.