The EU is funding the BREATH-EC project with ten million euros: A new immune cell therapy aims to halt pulmonary fibrosis and specifically inhibit scarring.
Prof. Dr. Nico Lachmann examines macrophages under a microscope. The photo shows the flags of the countries participating in the project. Copyright: Karin Kaiser/MHH
In pulmonary fibrosis, the tissue between the small alveoli becomes scarred, and as the disease progresses, progressive shortness of breath occurs due to stiffening of the lungs; a lung transplant may even become necessary. Pulmonary fibrosis is not yet curable. The causes are often unknown, and the clinical presentations vary widely. To date, treatments have been limited to slowing the progression of the disease. Ideally, the scarring and stiffening can be halted. However, it is usually not possible to reverse tissue damage that has already occurred.
A research team at Hannover Medical School (MHH) is now working intensively on new, effective treatment options as part of the new BREATH-EC project—in collaboration with other university hospitals and companies from Germany, Sweden, England, South Korea, Portugal, Ireland, Italy, and Belgium. From Germany, the Helmholtz Centre for Infection Research (HZI), the Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), and the University Medical Center Freiburg are participating. The European Union (EU) is funding this project with approximately ten million euros. Of this amount, the MHH will receive 2.73 million euros. The project is scheduled to run for four years.
“Our goal is to use certain immune cells to halt the progression of pulmonary fibrosis and possibly even reverse it. To do this, we are using genetically modified macrophages,” says Prof. Dr. Nico Lachmann of the Clinical Department of Paediatric Pneumology, Allergology and Neonatology at MHH. He is coordinating the four-year EU collaborative project.
Immune cells recognize and inhibit fibrosis
Macrophages—also known as “scavenger cells”—play a central role in the human immune system. They are essential for defending against pathogens and for repairing damaged tissue. The research team generates these macrophages from so-called induced pluripotent stem cells (iPS cells) or isolates them from donor blood. “We then genetically modify the macrophages. This enables them to both recognize early signs of fibrosis in the lungs and directly counteract them,” explains Professor Lachmann. “The macrophages intercept signaling molecules that promote fibrosis and produce antibodies on site that inhibit fibrosis.”
The long-term goal of the project is to administer the genetically modified macrophages to patients via bronchoscopy. This approach aims to halt—and possibly even reverse—fibrosis in the lungs, at least in the early stages of the disease. Furthermore, the research findings are expected to benefit the development of other innovative therapies for fibrotic diseases, including those affecting the liver and heart.
Cell and gene therapies for lung diseases
Macrophages are versatile immune cells that occur in the lungs, among other places, as alveolar macrophages in the alveoli. There, they orchestrate inflammatory processes and regulate various cell types. The research team is leveraging the unique function of macrophages and aims to have the optimized cells restore balance to the dysregulated inflammation. This type of cell therapy is conceivable for various lung diseases. This is because the ability to equip immune cells with novel, therapeutically relevant genes—and thereby enhance them—offers a wide range of applications. The BREATH-EC project thus fulfills a central goal of the German federal government’s High-Tech Agenda in the field of cell and gene therapies, as well as that of the Centre for Gene and Cell Therapy at MHH.
The Lower Saxony Ministry of Science and Culture provided financial support for the grant application. Professor Lachmann is a researcher in the RESIST Cluster of Excellence and at the German Center for Lung Research (DZL) in Hanover at the MHH. At the DZL, he investigates the function of macrophages in various lung diseases to develop new cell and gene therapy methods specifically targeting phagocytes.
In addition to Professor Lachmann, the BREATH-EC project at MHH also includes PD Dr. Ruth Olmer, Prof. Dr. Ulrich Martin, Prof. Dr. Ulrich Maus, and Prof. Dr. Jonas Schupp. Together with the other partners in the international consortium, they are advancing this novel therapeutic approach.
Text: Bettina Bandel