Pancreatic cancer treated in mice by loading tumour cells with tetanus - New Scientist

A new type of therapy aims to exploit immunity gained from childhood tetanus vaccinations to make the immune system attack hard-to-treat pancreatic cancer

Health 23 March 2022

By Alice Klein

Microscope image of a mouse pancreatic tumour – red spots are listeria bacteria delivering tetanus to tumour cells.

Claudia Gravekamp, Albert Einstein College of Medicine

Pancreatic tumours have been drastically shrunk in mice using a creative new strategy that allows the immune system to find and kill the cancer cells. The same approach may help to treat this notoriously deadly disease in people.

At the moment, most people diagnosed with pancreatic cancer only survive for a matter of months. This is because the cancer often spreads widely before symptoms arise and we lack effective treatments.

Many other cancers can be treated using immunotherapies that boost the natural cancer-fighting abilities of the immune system. However, these don't usually work for pancreatic cancer because it lacks the mutations that allow the immune system to detect it easily. Making matters worse, pancreatic tumours tend to be surrounded by cells that suppress immune activity.

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Claudia Gravekamp at Albert Einstein College of Medicine in New York and her colleagues wanted to make it easier for the immune system to detect and destroy pancreatic cancer. To do this, they developed an approach that uses listeria bacteria, which are naturally attracted to tumours, to selectively deliver an inactivated form of tetanus toxin to pancreatic cancer.

Because most of us are vaccinated against tetanus in childhood, our immune systems can detect it for the rest of our lives. This means pancreatic cancer cells that have been loaded up with tetanus should become visible to the immune system and therefore vulnerable to attack.

To test this, the researchers gave tetanus vaccines to young mice that were engineered to develop pancreatic cancer when they got older. When the mice developed advanced pancreatic cancer, tetanus-containing listeria bacteria were injected into their abdomens.

The bacteria successfully delivered the tetanus to the pancreatic tumours, making them visible to the immune systems of the mice. Immune cells called T-cells then started attacking the tumours.

The attack was amplified by giving the mice a drug called gemcitabine that stopped some of the cells around the pancreatic tumours from suppressing immune activity.

This treatment combination reduced the size of both the original pancreatic tumours and those that had spread to other parts of the body by over 80 per cent. It also improved the average survival time of the mice by 40 per cent compared with untreated mice.

Listeria is normally thought of as a food-poisoning pathogen, but the listeria used in the study was a weakened form that is non-toxic, says Gravekamp. The mice showed no significant side effects from the treatment.

Gravekamp and her colleagues are now organising a clinical trial to test if the weakened listeria can be safely injected into people's abdomens. If so, they hope to test the tetanus-containing listeria in people with pancreatic cancer.

The same approach may also help to treat other cancers that aren't easily detected by the immune system. For example, the researchers have tested the same tetanus-containing listeria in mice with ovarian cancer and found "very, very promising results", says Gravekamp. They want to turn their attention to bowel and brain cancer next, she says.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.abc1600

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