GM bugs could fight cancer

Genetically engineered bacteria could become the latest weapons against cancer, Cancer Research UK scientists suggest in a new study¹.

The authors found that infecting tumours with modified forms of E. coli – famous for causing food poisoning but normally harmless – could be a safe and highly effective way of attacking cancer cells.

Scientists killed cancer cells by using bacteria to sneak protein molecules inside them. There had previously been no method for doing this, because the molecules tend to get barred from entering cells or broken down before they can take action. But using bacteria seems to get around both these problems and could be a quick and easy way of reaching tumours.

E. coli bacteria are found naturally in the human gut and only a few strains are harmful. In the new study, scientists from the Cancer Research UK Molecular Oncology Unit at Barts and The London, Queen Mary’s School of Medicine and Dentistry, used E. coli that had been modified so they could no longer grow, divide or cause disease.

Researchers engineered the bacteria with a gene called invasin, allowing them to do something that normal E. coli cannot do – enter human cells by passing through their outside membranes. The bacteria also received a second gene, called listeriolysin O, to ensure they successfully released their cargo within cancer cells.

Dr Georges Vassaux, lead researcher at the Cancer Research UK Molecular Oncology Unit, says: “It’s notoriously difficult to get some types of therapeutic molecule inside cancer cells, which is why we turned to living organisms to do the job for us.

“With a few important genetic modifications, we were able to turn bacteria into efficient delivery capsules, able to penetrate the outside membrane of cancer cells and protect their precious cargo until safely inside.”

Using the bacteria, they were able to effectively deliver an enzyme called purine nucleoside phosphorylase into cancer cells. This turns an inactive ‘prodrug’ called 6-MPDR into a potent cancer treatment.

Over 90 per cent of cells invaded by bacteria were killed by MPDR, compared with less than 15 per cent of non-invaded cells.

When researchers targeted mouse tumours with the same combination of bacteria and drug, they found that the treatment seemed to slow the cancer’s progression and cause large numbers of tumour cells to die.

Dr Vassaux adds: “We may be able to use the bacterial system to reach as many cancer cells as possible with drug-activating enzymes. Subsequent prodrug treatment could then efficiently attack tumours while leaving healthy tissue alone – minimising side effects.

“We also think that introducing bacteria into a patient’s body, albeit harmless, neutered ones, will provoke the immune system and help to direct it against the tumour. So we may get the advantage of an immunotherapeutic effect, as well as the specific action of the prodrug treatment.”

Professor Robert Souhami, Cancer Research UK’s Director of Clinical and External Affairs, says: “Developing new drugs tends to grab the headlines, but equally important is the development of new systems to efficiently deliver treatments to cancer cells.

“Using bacteria to treat tumours is an innovative new approach to the problem and may offer the potential to target cancer cells with a range of different therapeutic molecules. It could open up exciting new avenues of cancer treatment.”

ENDS

1. Gene Therapy advance online publication, April 22, 2004