The study was designed to evaluate whether
TAPET-CD, an attenuated strain of Salmonella typhimurium expressing Escherichia coli
cytosine deaminase (CD), was capable of converting nontoxic
5-fluorocytosine (5-FC) to the active
antitumor agent 5-fluorouracil (5-FU). The antitumor effect of
TAPET-CD plus 5-FC against subcutaneously implanted colon
tumors was also evaluated.
TAPET-CD was given to
tumor-bearing mice by a single bolus
intravenous administration followed with 5-FC by intraperitoneal administration.
TAPET-CD accumulated in
tumors at levels 1000-fold higher than that in normal tissues and high levels of
5-FU were detected in
tumors in mice treated with both
TAPET-CD and 5-FC. No
5-FU could be detected in normal tissues. Inhibition of
tumor growth was observed in mice treated with either
TAPET-CD alone or
TAPET-CD in combination with 5-FC (
TAPET-CD/5-FC), but not with 5-FC alone.
TAPET-CD/5-FC inhibited
tumor growth by 88%-96%, compared to
TAPET-CD alone, which inhibited
tumor growth by 38%-79%. These data suggest that
tumor-targeting Salmonella could be used to deliver
prodrug-converting
enzyme selectively to
tumors and produced anti-
tumor effects when the corresponding
prodrug was also given.