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9 Feb 2010

Story ideas from the Journal of Biological Chemistry

- 28 Dec 2007
By American Society for Biochemistry and Molecular Biology   
Page 1 of 2

Turning anthrax toxin into a cancer killer


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After binding to cell surface markers, the MMP-activated PA protein (PA-L1) is cleaved by surface associated MMPs, releasing the PA20 fragment. The remaining receptor-bound fragment rapidly oligomerizes to form a...
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Most people wouldn’t consider anthrax toxin to be beneficial, but this bacterial poison may someday be an effective cancer therapy. Anthrax toxin has actually been shown to be fairly selective in targeting melanoma cells, although the risk of non-cancer toxicity prevents any clinical use.

To develop a better and safer treatment, Stephen Leppla and colleagues created a mutated antrax toxin that could only be turned on by matrix metalloproteinases (MMP), proteins that are overproduced only in cancer cells.

When they tested this mutated toxin in mice, the researchers observed that 100% of the animals tolerated a dose that would be lethal for the natural toxin. The MMP-toxin was also better at killing melanoma tumors than natural toxin, due to its higher specificity and longer half-life in the blood.

 
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