Breakthrough could ‘unleash’ potential of salmonella bowel cancer treatment

Salmonella could be engineered to help fight bowel cancer after researchers pinpointed how the bacteria stops the body’s own immune cells attacking the disease.

Experts have long known that salmonella could help beat cancer but when used in therapies it has not been as effective as hoped.

Now, experts have discovered that salmonella has been depleting a key protein which the body’s own immune cells need to function.

It is hoped the discovery can overcome the problem and help “unleash the full potential” of using salmonella to fight cancer.

It’s particularly rewarding to turn a disease-causing bug like salmonella into one that combats cancer

Researchers said there is “clinical interest” in combining bacterial therapies with immune checkpoint inhibitors, drugs that block proteins that regulate the immune system to allow T cells – a type of white blood cells that protects the body from infection and disease – to kill cancer cells.

However, the response from T cells to salmonella cancer therapies was “largely unknown”, they added.

Using mice, the team found salmonella stopped T cells from fighting cancer cells.

This was down to the bacteria depleting an amino acid called asparagine.

It is now hoped the discovery can lead to salmonella being engineered to not attack the protein, allowing T cells to work against tumour cells.

Dr Alastair Copland, first author of the study and research fellow in immunology at the University of Birmingham, said: “Bacterial therapies are an exciting way to treat cancer by essentially starving tumours of vital nutrients.

“One longstanding mystery has been why T cells, which are key to fighting cancer, don’t function optimally during this treatment.

“Now, we’ve identified the protein responsible for this, and pinpointed an exciting genetic target that could help us unleash the full potential of this therapy.

“It’s particularly rewarding to turn a disease-causing bug like salmonella into one that combats cancer.”

Salmonella can cause food poisoning and can be present in the guts of many animals, including chickens, cows and pigs.

We believe this knowledge could enable bacteria to be engineered not to attack asparagine allowing the T cells to act against the tumour cells leading to new effective treatments for cancer

The bacteria can contaminate food like eggs, chicken and pork, as well as fruits and vegetables that have been in contact with livestock or manure.

Symptoms of a salmonella infection include diarrhoea, stomach cramps, nausea, vomiting and fever, and usually develop within 12 to 72 hours and last from four to seven days.

Lead researcher Dr Kendle Maslowski, of the Cancer Research UK Scotland Institute in Glasgow and the University of Glasgow, added: “We know attenuated salmonella and other bacteria have the power to tackle cancer, however until now it was not known why it was not proving as effective as it should be.

“Our research has discovered that it is an amino acid called asparagine that the bacteria attacks which is essential for T cells to be activated.

“We believe this knowledge could enable bacteria to be engineered not to attack asparagine allowing the T cells to act against the tumour cells leading to new effective treatments for cancer.”

There are more than 44,000 new cases of bowel cancer each year in the UK, making it the fourth most common.

Cancer Research UK funded the study, published in the journal EMBO Molecular Medicine.

Dr Catherine Elliott, director of research at the charity, said: “Bacterial therapies have not become mainstream despite the massive strides we are making with immunotherapies which use our own bodies’ immune system to attack cancer.

“But the power of bacteria has long been acknowledged as likely to hold significant potential to tackle disease.

“This exciting development from the Cancer Research UK Scotland Institute could lead to more effective treatments for patients with colorectal, and other cancers in future, providing hope for patients.”