Abstract 588: Effect of antibiotic treatment on Salmonella typhimurium A1-R tumor targeting of prostate cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.588-588
• Main Authors: Zhao, Ming, Geller, Jack, Liu, Fang, Zhang, Lei, Zhang, Yong, Hoffman, Robert M.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-588

We have previously demonstrated that a genetically-altered Salmonella typhimurium, auxotrophic for arginine and leucine, could effectively treat metastatic PC-3 tumors in nude mice and profoundly increase survival. The auxotrophic mutations, induced by nitrosoguamidine, allow the bacteria to grow in tumors but not in normal tissue. Since human prostate cancer eventually becomes non-androgen-dependent similar to PC-3 tumors, bacterial treatment offers a novel treatment for this disease. In the current study, we observed the effect of antibiotic treatment on A1-R bacteria therapy of PC-3 tumors in nude mice. Thirty mice were implanted subcutaneously with PC-3 tumors expressing GFP. Approximately two weeks following implantation, the tumors were externally imageable. Ten of the 30 mice served as untreated control, and 10 mice were given A1 weekly intravenously as treated controls. Ten mice were given A1 intravenously weekly, combined with Gentamicin administered by intra-peritoneal injection at 100 µg daily for 10 day cycles with a two-day break between cycles. The treatment was repeated until the study end. Tumor growth was externally imaged by GFP expression of the tumors. All mice in the untreated group were sacrificed by 6 weeks after tumor implantation due to tumor size of 1.5-2.0 cm diameter. All mice in the A1-R-antibiotic combination group were sacrificed at 8 weeks due to tumor size. At the same time, all mice in the A1-R-only treatment group were alive and well. Currently, 3 treated mice were close to tumor eradication at 16 weeks following implantation and are still being injected weekly with A1-R. These results suggest that the tumor-targeting activity of A1-R bacteria was antibiotic dependent. This study gives proof of principle that A1-R can be regulated by antibiotics, an important safety feature for clinical application. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 588.