Biodistribution and Genetic Stability of the Novel Antitumor Agent VNP20009, a Genetically Modified Strain of Salmonella typhimurium

• Published in: The Journal of infectious diseases 2000-06, Vol.181 (6), p.1996-2002
• Main Authors: Clairmont, C., Lee, K. C., Pike, J., Ittensohn, M., Low, K. B., Pawelek, J., Bermudes, D., Brecher, S. M., Margitich, D., Turnier, J., Li, Z., Luo, X., King, I., Zheng, L. M.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Bacteria; Biological and medical sciences; Blood; Cancer; General aspects; Health care administration; Liver; Macaca fascicularis; Major Article; Medical sciences; Mice; Mice, Inbred C57BL; msbB gene; Pharmacology. Drug treatments; purI gene; Salmonella; Salmonella typhimurium; Salmonella typhimurium - genetics; Spleen; Tissue Distribution; Tumors
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315497

VNP20009 is a genetically modified strain of Salmonella typhimurium possessing an excellent safety profile, including genetically stable attenuated virulence (a deletion in the purI gene), reduction of septic shock potential (a deletion in the msbB gene), and antibiotic susceptibility. VNP20009 is genetically 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 10⁴ cfu/mL to undetectable levels in 24 h. In tumor-bearing mice, VNP20009 accumulates preferentially in tumors over livers at a ratio of 1000 : 1. In nonhuman primates, VNP20009 was also rapidly cleared from the blood, from a peak level of 1.0 X 10⁶ cfu/mL to undetectable levels in 24 h. VNP20009 was detected in the liver, spleen, and bone marrow of monkeys; the amount decreased over time, and VNP20009 was cleared from all organs by day 41; no VNP20009 could be detected in the urine or feces of the monkeys. VNP20009 is genetically stable after many generations of growth >140) both in vitro and in vivo.