Dangerous fungal lung infections could be treated with CAR T-cells

Adapted immune cells known as CAR T-cells could treat lungs infected by the fungus Aspergillus fumigatus in people with suppressed immune systems, a study in mice suggests

By Carissa Wong

Aspergillus is a black mould that can cause pulmonary infection

Shutterstock/Kateryna Kon

Life-threatening fungal lung infections could be treated with modified immune cells known as CAR T-cells, a study in mice suggests.

People often breathe in a fungus called Aspergillus fumigatus that is commonly found in the air and soil. When we are healthy, our immune systems can normally clear any fungus out of the lungs before it causes harm.

However, in people with suppressed immune systems – which can result from cancer treatment or receiving transplants, for example – the fungus can grow in the lungs, causing breathlessness and, in extreme cases, death.

This condition, called invasive pulmonary aspergillosis, is often treated using antifungal drugs, but such medicines can damage the kidney and liver, and don’t always work against some variants of A. fumigatus.

In search of an alternative treatment, Michael Hudecek at University Hospital Würzburg in Germany and his colleagues took immune cells called T-cells that had been donated by people without immune system issues. They then modified them to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs bind to proteins on the fungus cell wall. The resultant cells, known as CAR T-cells, can track down and kill invasive cells once infused into the body.

To test if the approach worked for the fungus, the team exposed mice with suppressed immune systems to A. fumigatus. The group then treated some mice with the CAR T-cells a day later and left the other mice untreated.

Two weeks after initial exposure to the fungus, 80 per cent of mice treated with CAR T-cells survived, while just 33 per cent of untreated mice were alive.

When the team analysed lung samples from the mice, animals treated with CAR T-cells had much less fungus in their lungs than the untreated mice.

“This study is an elegant application of cellular immunotherapy to a difficult-to-treat infection that causes substantial morbidity and mortality in immune-compromised humans,” says Tobias Hohl at Memorial Sloan Kettering Cancer Center in New York.

However, further work is needed to test the approach before we know if CAR T-cells could treat A. fumigatus infections in people, he says.

We need to establish if the CAR T-cells would confer a benefit when mice or humans are being treated with immune-suppressing therapies used in conjunction with transplants or chemotherapy, says Hohl.

Ideally, any treatment for fungal infections along these lines used in people would adapt someone’s own T-cells to maximise the chances of it working, but those with weakened immune systems might not have sufficient T-cells for this, says Hohl.

Freezing CAR T-cells derived from other people could help to address this issue, say the study authors in their paper.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.abh1209

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