Salmonella typhimurium A1-R (A1-R) is auxotrophic for arg and leu, which attenuates growth in normal tissue but allows high tumor 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 a Phase I clinical trial, but has more attenuation mutations than A1-R. Lewis-lung mouse lung cancer-bearing mice were treated with A1-R and VNP20009 in nude mice. A1-R and VNP20009 were both eliminated from the liver and spleen approximately 3-5 days after administration via tail vein, however A1-R showed higher tumor targeting and increased mouse survival than VNP20009 with less body weight loss. The mice tolerated A1-R at least 2-fold higher than NVP20009 when bacteria were administered iv. The results of the present study suggest that A1-R has greater clinical potential than VNP20009.
Citation Format: Yong Zhang, Nan Zhang, Robert M. Hoffman, Ming Zhao. Comparison of Salmonella typhimurium A1-R and VNP20009 on the Lewis Lung carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 704. doi:10.1158/1538-7445.AM2014-704