Single Infusion of Long-Lived Multifunctional T Cells with IL4 Mutations Can Provide Lasting Relief for Asthma

In a new study, researchers from Tsinghua University in China found that genetically modified long-lived multifunctional T cells can inhibit the symptoms and signs of allergic asthma in mice for up to a year. Specifically, they genetically modified CAR-T cells to reduce the function of interleukins associated with type 2 high characteristic asthma. The relevant research results were published in the Nature Immunology journal, titled "A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice".

Asthma is a disease characterized by inflammation, narrowing, and swelling of the airways. As a reaction, the lungs produce excessive mucus, leading to difficulty breathing. The usual method of treating this disease is to use inhalers that can alleviate inflammation. Both healthcare workers and patients hope for better treatment plans. In this new study, these authors may have found such a treatment option.

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These authors focus on alleviating the symptoms of type 2 high characteristic asthma, which is typically associated with an increase in eosinophils driven by interleukin-5 (IL-5), which leads to increased mucus secretion.

CAR-T cells are most commonly associated with anti-cancer. However, they noted that it is likely to help treat other diseases such as asthma. They utilized IL-5 as a targeted domain and eliminated BCOR and ZC3H12A to design long-lived CAR-T cells that can eliminate eosinophils. They refer to these cells as immortal functional IL-5 CAR-T cells (5TIFs). They further modified 5TIF cells to secrete an IL-4 mutant protein that can block IL-4 and IL-13 signaling, hence the name 5TIF4 cells. In the asthma model, a single infusion of 5TIF4 cells in fully immunocompetent mice can continuously suppress lung inflammation and alleviate asthma symptoms without any conditioning regimen.

These authors subsequently monitored the health status of these test mice for up to a year. They found that 5TIF4 cells continued to exist in mice, and their presence led to sustained relief of asthma symptoms. These data indicate that asthma, a common chronic disease, can be alleviated in the long term through a single dose of long-lived CAR-T cells.

Reference Gang Jin et al. A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice. Nature Immunology, 2024, doi:10.1038/s41590-024-01834-9.

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