Scientific Publications by FDA Staff

Cancer Res 2007 Jun 15;67(12):5859-64

Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs.

Zhang L, Gao L, Zhao L, Guo B, Ji K, Tian Y, Wang J, Yu H, Hu J, Kalvakolanu DV, Kopecko DJ, Zhao X, Xu DQ

Zhao XJ (reprint author), Jilin Univ, Dept Pathophysiol, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Xinmin St, Changchun 130021, Peoples R China Jilin Univ, Dept Pathophysiol, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Changchun 130021, Peoples R China Univ Maryland, Sch Med, Dept Microbiol & Immunol, Program Mol Biol,Greenebaum Canc Ctr, College Pk, MD 20742 USA Univ Maryland, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD USA

The facultative anaerobic, invasive Salmonella enterica serovar typhimurium (S. typhimurium) has been shown to retard the growth of established tumors. We wondered if a more effective antitumor response could be achieved in vivo if these bacteria were used as tools for delivering specific molecular antitumor therapeutics. Constitutively activated transcription factor signal transducer and activator of transcription 3 (STAT3) promotes the survival of a number of human tumors. In this study, we investigated the relative efficacies of attenuated S. typhimurium alone or combined with Stat3-specific small interfering RNA (siRNA) in terms of tumor growth and metastasis. The bacteria preferentially homed into tumors over normal liver and spleen tissues in vivo. S. typhimurium expressing plasmid-based Stat3-specific siRNAs significantly inhibited tumor growth, reduced the number of metastastic organs, and extended the life time for C57BL6 mice bearing an implanted prostate tumor, versus bacterial treatment alone. These results suggest that attenuated S. typhimurium combined with an RNA interference approach might be more effective for the treatment of primary as well as metastatic cancer.