The Pharmaceutical Journal
Vol 270 No 7235 p181
8 February 2003

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Engineered anthrax toxin has efficacy against tumours

An anthrax toxin that has broad and potent antitumour activity but exerts limited toxicity to normal tissue has been produced by American researchers.

Dr Shihui Liu, National Institutes of Health, Bethesda, Maryland, and colleagues designed a version of the toxin that is activated in vivo by cell-surface urokinase plasminogen (uPA).

They explain that uPA is an attractive target for the treatment of cancer and show that by changing the specificity of protease activation, anthrax toxin can be converted from a highly lethal toxin to an agent with potent antitumour activity.

The toxin displayed potent cytotoxicity to a spectrum of transplanted tumours of widely different origins — including connective tissue, neural crest and pulmonary epithelium — and eradicated established tumours in mice. Antitumour activity depended on tumour cell-surface plasminogen activation, they say.

The researchers conclude: "This engineered toxin efficiently suppressed malignant tumour growth and could eradicate established tumours in the absence of toxicity to normal tissue. The engineered toxin may have broad applicability for the treatment of human tumours because of its species-independent mode of activation and the copious expression of cell-surface uPA on human tumours, ranging from carcinoma and sarcoma to hematogenous malignancies."

They add that the engineered toxin has the potential to be modified for diagnostic imaging of human tissue.

The study is published in Proceedings of the National Academy of Sciences (2003;100:657).