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: Yong Zhang, Nan Zhang, Ming Zhao, Robert M Hoffman
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 16 Pg. 14625-31 (Jun 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25714030 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bacterial Vaccines
• VNP 20009

Topics

• Animals
• Bacterial Vaccines (pharmacology, therapeutic use)
• Carcinoma, Lewis Lung (drug therapy, pathology)
• Cell Line, Tumor
• Disease Models, Animal
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Mice
• Mice, Nude
• Salmonella typhimurium (drug effects)
• Xenograft Model Antitumor Assays