WITH the help of a little genetic tinkering, a humble soil bacterium could become the latest recruit in the war on cancer.
It is now over a century since physician William Coley noticed that some of his patients with bacterial infections were able to fight off cancer. The reasons why this sometimes works have never been clear, though it possibly involves stimulating the immune system (New Scientist, 2 November 2002, p 54).
Later experiments inspired by this work, however, showed that Clostridium bacteria thrive in cancerous tissues. They need low-oxygen conditions, and the tightly packed cells and poor blood supply of most tumours make them an ideal habitat. But tests in animals were disappointing. Although the bacteria would usually destroy most of a tumour, a ring of cancerous tissue around the edge usually survived.
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Now Nigel Minton at the University of Nottingham in Britain is trying to overcome this problem by combining the bacterial treatment with the 鈥減rodrug鈥� approach, in which patients are given a harmless precursor drug that is only activated in cancerous tissue. The tricky part is getting the enzyme that activates the precursor into the tumour.
One approach has been to attach the enzyme to an antibody that binds only to cancer cells, but this means finding antibodies for each tumour type. Instead, Minton has added an extra loop of DNA carrying the gene for the enzyme to a harmless strain of Clostridium. The bacteria deliver the enzyme to the tumour, and they are not fussy about what sort of tumour it is, he told the Society for General Microbiology meeting in Edinburgh last week. So after the precursor drug is injected into the bloodstream of patients, tumours should be destroyed from the inside, leaving healthy tissues unharmed.
One worry is that the bacteria might reach other low-oxygen parts of the body such as the gut, though this didn鈥檛 happen in tests on mice. Nor is it yet clear if small tumours will have too much oxygen for the bugs to survive, admits team member Philip Burke of Enact Pharma in Salisbury. Initial trials in patients should soon provide the answers.