The last step, which the biologists haven’t yet started, will be to engineer the bacteria to produce an enzyme that converts a drug precursor into a cancer-killing compound. The patient would take a pill containing the precursor, which would be converted into the active drug only inside the bacterially infected cancer cells.
“The bacteria are engineered to sense cells and then invade – that’s a unique demonstration of what you can do by programming cells,” says James Collins, a biomedical engineer at Boston University (who was not involved in the project).
Anderson and colleagues still face many technical and safety hurdles before they have a viable bacterial cancer treatment. For example, the human immune system attacks bacteria when they’re injected into the bloodstream. So the researchers engineered the bacteria to produce a special lipid coating that makes the organism invisible to part of the immune system.
The team is also designing a series of safeguards into the system. Patients could develop sepsis, for example, if the bacteria reproduced too quickly in the blood. Previous research has shown that bacteria need iron from human blood to grow and reproduce. So the scientists deleted a certain gene that allows the organisms to extract iron from the blood, which should drastically limit bacterial growth inside the body.
While the idea of bacterial therapies may sound highly experimental – and even frightening – it has existed for at least a century, and it’s already been put into practice. The Bacillus Calmette-Guerin (BCG) vaccine, a preventative treatment for tuberculosis made from a live but weakened version of the tuberculosis bacterium, is also effective in treating bladder cancer when injected directly into the bladder. Use of this therapy, however, is limited to cancers lining the surface of the bladder, because the bacteria can easily access these cancer cells.
In addition, some strains of bacteria have a natural affinity for tumor cells, a quality that scientists have tried to take advantage of when designing new therapies. Vion Pharmaceuticals, based in New Haven, CT, is developing a cancer treatment centered on the salmonella bacteria, which have this property. Anderson’s bacteria work differently, though: they actively target tumor cells through the invasin protein, rather than relying on the bacteria’s natural mechanism, and therefore may be less sensitive to differences in tumor types.
Still, the latest work is likely to require a lot of scrutiny from the Food and Drug Administration. Anderson emphasizes that, at least at first, these bacteria would be given only to people who’ve failed to benefit from other treatments.