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
|