salmonella typhimurium , a facultative anaerobe , has been shown to accumulate at tumor sites when injected intravenously into mouse tumor models
attenuated s. typhimurium were engineered to express fas ligand ( fasl ) to deliver this toxic , antitumor cytokine to tumor sites and to thereby enhance therapeutic potential .
s. typhimurium expressing fasl dramatically inhibited the growth of d2f2 murine breast carcinoma and ct-26 murine colon carcinoma tumors , as well as the growth of d2f2 pulmonary metastases in mice .
these experiments involved murine tumor models , and the effects of fasl - expressing s. typhimurium on human tumor models are not yet known .
salmonella typhimurium , a facultative anaerobe , has been shown to accumulate at tumor sites when injected intravenously into mouse tumor models
attenuated s. typhimurium were engineered to express fas ligand ( fasl ) to deliver this toxic , antitumor cytokine to tumor sites and to thereby enhance therapeutic potential .
s. typhimurium expressing fasl dramatically inhibited the growth of d2f2 murine breast carcinoma and ct-26 murine colon carcinoma tumors , as well as the growth of d2f2 pulmonary metastases in mice .
these experiments involved murine tumor models , and the effects of fasl - expressing s. typhimurium on human tumor models are not yet known .
nih - ca69381 ; austrian program for advanced research and technology ( austrian academy of sciences ) .
 intravenous administration of bacteria leads to their accumulation in tumors and to sporadic tumor regression . 
 we therefore explored the hypothesis that salmonella typhimurium engineered to express the proapoptotic cytokine fas ligand ( fasl ) would exhibit enhanced antitumor activity . 
 immunocompetent mice carrying tumors derived from syngeneic murine d2f2 breast carcinoma or ct-26 colon carcinoma cells were treated intravenously with fasl - expressing s. typhimurium or with phosphate - buffered saline ( pbs ; control ) . 
 treatment with fasl - expressing s. typhimurium inhibited growth of primary tumors by an average of 59% for d2f2 tumors and 82% for ct-26 tumors 
 ( eg , at 25 days after initial treatment , mean volume of pbs - treated ct-26 colon carcinomas = 1385 mm3 and of s. typhimurium fasl - treated ct-26 tumors = 243 mm3 , difference = 1142 mm3 , 95% confidence interval = 800 mm3 to 1484 mm3 , p < .001 ) . pulmonary d2f2 metastases ( as measured by lung weight ) were reduced by 34% in s. typhimurium fasl - treated mice compared with pbs - treated mice . 
 fasl - expressing s. typhimurium had similar effects on growth of murine b16 melanoma tumors in wild - type mice but not in lpr / lpr mice , which lack fas , or in mice with disrupted host inflammatory responses . 
 antitumor activity was achieved without overt toxicity . 
 these preclinical results raise the possibility that using attenuated s. typhimurium to deliver fasl to tumors may be an effective and well - tolerated therapeutic strategy for some cancers . 
CONTEXT AND CAVEATS
Prior knowledge
Study design
Contribution
Implications
Limitations
Funding
Supplementary Material