Ajou University Researchers Unveil Groundbreaking Treatment for Severe Eosinophilic Asthma
Ajou University Professor Hae-sim Park, together with Yong-seong Kim’s research team, has made an exciting breakthrough in the development of cutting-edge treatments. Their recent research findings suggest the possibility of a new treatment for severe eosinophilic asthma using a T-cell engagement dual antibody (Engager).
The double T-cell engaging antibody is an immunotherapy drug that brings cancer cells and T-cells in close proximity, triggering the T-cells to destroy the cancer cells. While it has been successfully utilized for acute lymphoblastic leukemia treatment since 2014, its application for other diseases has not been widely reported.
Working diligently on this project, Professor Hae-sim Park and Professor Yong-seong Kim’s teams at Ajou University Hospital’s Department of Allergy and the Department of Molecular Science and Technology at Ajou University College of Engineering, respectively, have developed a novel dual antibody treatment. This treatment targets eosinophils using the patient’s T-cells in severe eosinophilic asthma.
Severe eosinophilic asthma is a particularly severe form of asthma characterized by an excessive increase in eosinophils due to allergic reactions, leading to asthma symptoms and respiratory dysfunction. Eosinophils, a type of white blood cell responsible for defending the body against parasitic infections, become inflammatory cells exacerbating asthma symptoms in severe eosinophilic asthma.
To address this, the research team aimed to inhibit the activity of inflammatory eosinophils and induce their cell death as a means of treating severe eosinophilic asthma. Currently, antibody treatments such as ‘reslizumab’ and ‘mepolizumab’, which neutralize the immune mediator interleukin-5 (IL5), and benralizumab, targeting IL5 receptor (IL-5Rα), are employed. However, while antibody treatments have proven effective for many patients, their impact is relatively low in some cases, necessitating the development of antibody treatments with new mechanisms.
Focusing on the specific expression of the IL5 receptor on eosinophil inflammatory cells, the research team developed a ‘dual target antibody’ that simultaneously targets the IL5 receptor and CD3, a T-cell marker. This antibody double enables the recognition of two different antigens with just one antibody molecule.
Through the cultivation of eosinophils and autologous T-cells using the blood of 11 healthy adults, the research team observed that the T-cells efficiently killed eosinophils within 24 hours of adding the double antibody.
Professor Hae-sim Park commented, “This study is significant as it suggests a new, effective treatment for severe eosinophilic asthma, a condition that poses a higher risk of death compared to general asthma.”
Echoing Professor Park’s sentiment, Professor Kim Yong-seong, the corresponding author of the research paper, stated, “For the first time, we have proposed that the development of a dual antibody treatment utilizing T-cells, previously limited to blood cancer treatment, may have relevance in severe eosinophilic asthma. We aim to contribute to treatment development through future clinical research.”
The research findings were published in the prestigious international academic journal Clinical Immunology under the title “Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of eosinophilic asthma and serious asthma” in September 2023, solidifying the importance and impact of this study.
This groundbreaking study was made possible with support from the Ministry of Health and Welfare’s hospital development research and development project.
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Ajou University Professor Hae-sim Park and Yong-seong Kim’s research team
Presents the possibility of developing new, cutting-edge treatments
Research results have been published that suggest the possibility of developing a T-cell engagement dual antibody (Engager) as a new treatment for severe eosinophilic asthma.
A double T-cell engaging antibody is an immunotherapy drug that brings cancer cells and T cells close together and prompts the T cells to kill cancer cells. Since it was first approved for acute lymphoblastic leukemia in 2014, it is currently in active development for cancer treatment, but has not been reported for other diseases.
On the 20th, the team of Professor Hae-sim Park from the Department of Allergy at Ajou University Hospital and the team of Professor Yong-seong Kim (graduate students Jun-ho Kim and Dae-seong Kim) from the Department of Molecular Science and Technology at Ajou University College of Engineering developed a dual antibody treatment using a new mechanism to remove eosinophils using the patient’s T cells in severe eosinophilic asthma.
Severe eosinophilic asthma is a representative form of severe asthma in which eosinophils increase excessively due to an allergic reaction, causing asthma symptoms and respiratory dysfunction.
Eosinophils are a type of white blood cell that mainly protects the body against parasitic infections, but in severe eosinophilic asthma, they act as inflammatory cells that make asthma worse.
Accordingly, research has been conducted to inhibit the activity of inflammatory eosinophils and induce their death to treat severe eosinophilic asthma.
Currently, ‘reslizumab’ and ‘mepolizumab’, which neutralize the immune mediator interleukin-5 (IL5), and benralizumab, which targets the IL5 receptor (IL-5Rα), are used such as antibody treatments for eosinophilic asthma, although antibody treatments are effective in many patients, the effect of the treatment is low in some patients, which means that antibody treatments with a new mechanism need to be developed.
Focusing on the fact that the IL5 receptor is specifically expressed on eosinophil inflammatory cells, the research team developed a ‘dual target antibody’ which simultaneously targets the IL5 receptor and CD3, a T cell marker. An antibody double is an antibody that can recognize two different antigens with one antibody molecule.
The research team revealed that when eosinophils and autologous T cells were cultured together using the blood of 11 healthy adults, they confirmed that the T cells killed eosinophils very efficiently 24 hours after the addition of the double antibody.
The newly developed IL5 receptor
Specifically, the IL5 receptor
Professor Hae-sim Park said, “This study is significant as it suggests a new effective treatment for severe eosinophilic asthma, which has a higher risk of death compared to general asthma.”
Professor Kim Yong-seong, corresponding author of the paper, said, “For the first time, we suggested that the possibility of developing a dual antibody treatment using T cells, which was previously limited to the treatment of blood cancer, may be relevant to severe eosinophilic asthma. “We will contribute to the development of treatments through clinical research in the future,” he said.
Meanwhile, this study was published in the international academic journal Clinical Immunology in September 2023, entitled ‘Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of eosinophilic asthma and serious asthma.’ It was published online under the title ‘Dual antibody development’.
This study was carried out with the support of the Ministry of Health and Welfare’s hospital development research and development project.
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