Oncotarget

Research Papers:

Comparison of the selective targeting efficacy of Salmonella typhimurium A1-R and VNP20009 on the Lewis lung carcinoma in nude mice

Yong Zhang, Nan Zhang, Ming Zhao _ and Robert M. Hoffman

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Oncotarget. 2015; 6:14625-14631. https://doi.org/10.18632/oncotarget.3342

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Abstract

Yong Zhang1, Nan Zhang1, Ming Zhao1 and Robert M. Hoffman1,2

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.


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