title: Comparison of the selective targeting efficacy of Salmonella typhimurium A1-R and VNP20009 on the Lewis lung carcinoma in nude mice.
abstract: Salmonella typhimurium A1-R is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor targeting and virulence. A1-R is effective against metastatic human prostate, breast, and pancreatic cancer as well as osteosarcoma, fibrosarcoma, and glioma in clinically-relevant mouse models. VNP20009 is also a genetically-modified strain of Salmonella typhimurium that has been tested in Phase I clinical trials, but is more attenuated than S. typhimurium A1-R and in addition of multiple amino-acid auxotrophs, is purine auxotropic with the purI mutation. In the present study, mouse Lewis lung carcinoma-bearing nude mouse models were treated with S. typhimurium A1-R or VNP20009. S. typhimurium A1-R and VNP20009 were both eliminated from the liver and spleen approximately 3-5 days after administration via the tail vein. However, A1-R showed higher tumor targeting and inhibited the Lewis lung carcinoma to a greater extent than VNP20009, with less body weight loss. The mice tolerated S. typhimurium A1-R to at a least 2-fold higher dose than VNP20009 when the bacteria were administered iv. The results of the present study suggest that S. typhimurium A1-R has greater clinical potential than VNP20009.
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.|Department of Surgery, University of California, San Diego, California, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D012486:Salmonella typhimurium / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001428:Bacterial Vaccines; C465023:VNP 20009
keywords: GFP; RFP; Salmonella typhimurium A1-R; VNP20009; lung cancer