In the war against cancer, we need new weapons. Bacteria could prove useful new recruits in the battle, armed with poisons and engineered to self-destruct after completing their mission.
Jeff Hasty and his team at the University of California, San Diego, used this method to slow the growth of tumours in mice, raising the promise that bacteria could attack the parts of tumours we find most difficult to target.
This idea was inspired by discoveries in recent years that have shown us just how many bacteria live inside our bodies – and even inside our tumours. Salmonella, for example, can survive without oxygen, so these bacteria are well-equipped to live in the anaerobic environment within a tumour. “It’s only natural that some bacteria have evolved to thrive in tumours,” says Hasty.
This offers a tantalising prospect. We currently use the blood vessels inside tumours as a way to deliver chemotherapy, but there is a problem: the innermost parts of a tumour have no blood vessels, rendering them untouchable.
The ability of Salmonella to live in these areas has inspired Hasty’s team to engineer strains of these bacteria to produce three types of cancer-killing drug: one that destroys cell walls, one that alerts the body’s immune system, and one that triggers cells to die. To release this toxic cocktail, the researchers programmed the bacteria to self-destruct and break open after a certain number of them had accumulated in the same spot. “It’s basically a kamikaze mission,” says Hasty.
The researchers found that when they fed mice that had liver tumours, their engineered bacteria travelled directly to the anaerobic regions of the tumours. When the mice were given bacteria that released all three drugs, their tumours stopped growing. And when they were given the bacteria in combination with chemotherapy, their tumours shrank in size, and their life expectancy increased by 50 per cent.
The idea of weaponising bacteria has been around for some time, says Bert Vogelstein at Johns Hopkins University in Baltimore, Maryland, who led one of the first experiments to try to harness bacteria as anti-cancer assassins 15 years ago. But every advance is good news, he says: being able to successfully deploy bacteria against things that attack the body would be a game changer.
In particular, this new method is the first to deliver drugs by programming bacteria to break apart and die. The technique not only releases the drugs, but also keeps the number of bacteria under control. “The major advance is that this is a way to provide sustained release of therapeutics in tumours,” says Neil Forbes at the University of Massachusetts Amherst.
Hasty says he does not know exactly how bacteria get to the liver tumours when fed to the mice, but he thinks they probably travel via the hepatic portal vein – a crucial route for blood travelling from the stomach to the liver.
This raises some concerns, says Elisabeth Bik, a microbiologist at Stanford University. How do they know the bacteria aren’t spreading around the body and causing collateral damage to healthy tissue, she asks.
Hasty says that the bacteria do seem to localise specifically to the insides of tumours, perhaps because they are sheltered there from a mouse’s immune system.
His idea is that such bacterial therapies could eventually be used in combination with existing drugs to attack tumours from both the inside and outside.
But the road to the final product could be long, cautions Bik. Although she thinks it is a promising clinical approach, mouse models may provide misleadingly optimistic results. “The kinds of tumours that mice grow may not be similar enough to the kinds of tumours humans grow,” she says. Lab mice are also engineered to have a genetic disposition to cancer, whereas environmental factors are often involved in the case of humans.
It may also be risky to give these strains to people. Even Salmonella strains that have reduced virulence can be pathogenic to us, says Bik.