Engineered CAR T cells repress signs and symptoms of allergic asthma in mice for a year

A team of molecular oncologists at Tsinghua University's State Key Laboratory of Molecular Oncology, in China, has found that engineered, long-lived and multifunctional T cells repress signs and symptoms of allergic asthma in mice for up to a year.

In their study, published in the journal Nature Immunology, the group engineered CAR T cells to reduce the functionality of interleukins associated with type 2 high-signature asthma.

Bart Lambrecht and Hamida Hammad, with the VIB-UGent Center for Inflammation Research, in Belgium, have published a New & Views piece in the same journal issue outlining the work done by the team.

Asthma is a condition in which airways become inflamed, narrow and swollen—as a reaction, the lungs produce excess amounts of mucus, making it difficult to breathe. The condition is typically treated with inhalers that reduce inflammation. Medical workers and patients would prefer a better treatment option. In this new effort, the team in China may have found one.

The researchers focused on reducing symptoms for type 2 high-signature asthma, which is typically associated with interleukin-5-driven eosinophilia, which drives increases in mucus production.

Engineering chimeric antigen receptor (CAR) T cells is most often associated with combating cancer, which is where the workers on this team usually focus their efforts. But they noted that such engineering efforts could likely help with other conditions, such as asthma.

To that end, they engineered CAR T 5T_IF and 4T_IF cells to make them secrete a IL-4 mutein known to block IL-4 and IL-13 signaling. They then injected the results into mice with induced human-like asthma.

The team then monitored the health of the test mice for up to a year—they found that 5T_IF and 4T_IF cells persisted in the bodies of the mice and that their presence resulted in continued reductions in asthma symptoms.

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