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Scientists have used genetically reprogrammed bacteria to destroy tumours in mice. The innovative method one day may lead to cancer therapies that treat the disease more precisely, without the side effects of conventional drugs.
The researchers already are scrambling to develop a commercial treatment, but success in mice does not guarantee that this strategy will work in people. Still, the new study, published on Wednesday in the journal Nature Medicine, is a harbinger of things to come, said Michael Dougan, an immunologist at Massachusetts General Hospital in Boston.
“At some point in the future, we will use programmable bacteria for treatment,” said Dougan, whose research laid some groundwork for the new study. “I think there’s just too much potential.”
Our immune cells can sometimes recognise and destroy cancer cells without assistance. But tumours may hide from the immune system by taking advantage of a gene called CD47.
Normally, the gene makes a protein that studs the surface of red blood cells, a kind of sign that reads, “Don’t Eat Me.” Immune cells see it, and pass by healthy red blood cells.
But as red blood cells age, they lose CD47 proteins. Eventually the immune cells no longer give them a free pass, gobbling up old cells to make way for new ones. Mutations in cancer cells can cause them to switch on the CD47 gene. The immune system sees these cells, too, as harmless, allowing them to grow into dangerous tumours.
In recent years, scientists have been developing antibodies that can attach to CD47 proteins on cancer cells, masking the “Don’t Eat Me” sign. Then the body’s immune cells learn to recognise the cancer cells as dangerous and attack.
But standard antibodies are big molecules that can’t burrow into a large tumour. And since they have to be injected into the bloodstream, these antibodies end up everywhere in the body, causing side effects. Nicholas Arpaia, an immunologist at Columbia University in New York, and Tal Danino, a synthetic biologist, wondered if they could use bacteria to turn the immune system against cancer cells — but from within tumours, rather than from outside.
Ordinary bacteria will colonise tumours in the body, using them as a refuge from the immune system. In 2016, Danino helped construct bacteria that can make drugs to fight tumours after entering them. Bacteria cannot make normal antibodies for CD47. But recently, Dougan and his colleagues developed a tiny version of the molecule called a nanobody. Not only are nanobodies small enough for bacteria to produce, they’re also much more potent than conventional antibodies.
The researchers inserted the nanobody gene into the bacteria, turning them into nanobody factories. Then the team injected five million of the altered microbes into mouse tumours.
The bacteria were also programmed to commit mass suicide. After they established themselves and multiplied, 90 percent of the bacteria ripped themselves apart, spilling out nanobodies. The nanobodies attached to CD47 proteins on the cancer cells, robbing them of their camouflage.