GM bacteria used as cancer treatment
means of delivering proteins into tumour cells and killing them,
raising the hope that this could form the basis of a new treatment
for cancer.
The scientists, from medical charity Cancer Research, report in an advance online publication on the Gene Therapy journal website that infecting tumours with genetically-modified forms of Escherichia coli could overcome the obstacles to delivering protein drugs to tumours.
E coliis found naturally in the human gut and is a well-recognised cause of food poisoning, although only a few strains are actually harmful. In the new study, scientists from Cancer Research UK and Queen Mary's School of Medicine and Dentistry in London used E coli that had been modified so they could no longer grow, divide or cause disease.
They engineered the bacteria with a gene called invasin, allowing them to do something that unmodified E coli cannot do - enter human cells by passing through their membranes. The bacteria also received a second gene, coding for a protein 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, said: "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."
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 toxic purine, 6MP, causing cell death. And because only the cancer cells absorb the enzyme, administration of 6-MDPR should not cause toxic effects in other cells.
In fact, the study found that over 90 per cent of cells invaded by bacteria were killed by 6-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.
Dr Vassaux noted that it may be 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."
