Comparison of the selective targeting efficacy ofSalmonella typhimuriumA1-R and VNP20009 on the Lewis lung carcinoma in nude mice

// Yong Zhang 1 , Nan Zhang 1 , Ming Zhao 1 and Robert M. Hoffman 1,2 1 AntiCancer, Inc., San Diego, California, USA 2 Department of Surgery, University of California, San Diego, California, USA Correspondence to: Robert M. Hoffman, email: // Keywords : lung cancer, Salmonella typhimurium A1-R, VNP20009, GFP, RFP Received : December 16, 2014 Accepted : January 03, 2015 Published : January 21, 2015 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.