TUM and UCSF Collaborate on Engineered Immune Cells to Target Inflammatory Disorders

TUM and UCSF Collaborate on Engineered Immune Cells to Target Inflammatory Disorders

(IN BRIEF) Researchers from UCSF and the Technical University of Munich (TUM) have developed engineered regulatory immune cells to precisely modulate the immune system, addressing conditions like type 1 diabetes, autoimmune diseases, and organ transplant rejection. Unlike traditional immunosuppressants, this approach targets immune overreactions locally, reducing side effects. Tested in mice with transplanted human islet cells, the technology successfully protected insulin-producing beta cells. It also holds promise for refining CAR T-cell cancer therapies and advancing stem cell treatments. The study, published in Science, reflects TUM’s focus on translating cutting-edge research into clinical applications through its Center for Organoid Systems (COS).

(PRESS RELEASE) MUNICH, 13-Dec-2024 — /EuropaWire/ — Researchers have developed engineered regulatory immune cells capable of precisely modulating the immune system to address conditions like type 1 diabetes, autoimmune diseases, and organ transplant rejection. Unlike traditional immunosuppressant therapies that suppress the entire immune system—leading to severe side effects such as heightened infection and cancer risk—this approach offers localized and targeted immune regulation.

A Precision Approach to Immune Regulation

The immune system plays a critical role in distinguishing between the body’s own cells and foreign invaders. However, when dysregulated, it can mistakenly attack healthy cells, as seen in type 1 diabetes, where insulin-producing beta cells in the pancreas are destroyed. To counter this, a team of scientists has engineered regulatory T cells that specifically protect healthy tissues by recognizing their antigens and preventing T-killer cells from attacking them. This innovation has the potential to eliminate the need for broad immunosuppression, instead providing targeted protection against immune overreaction.

“This technology can restore balance to the immune system,” said Wendell Lim, PhD, professor of cellular and molecular pharmacology at UCSF. “We envision it as a platform for addressing a wide range of immune dysfunctions.”

From Research to Real-World Applications

The research, led at UC San Francisco (UCSF) with substantial contributions from Professor Matthias Hebrok and Dr. Hasna Maachi of the Technical University of Munich (TUM), was recently published in the journal Science. The team’s approach leverages the same cellular framework used in CAR T-cell immunotherapy, which targets tumor cells. However, these engineered regulatory immune cells are designed to safeguard healthy cells by producing proteins with anti-inflammatory properties and scavenging pro-inflammatory substances. The system’s versatility allows for adaptation to various medical applications.

Promising Results in Type 1 Diabetes

To test their solution, researchers modified the regulatory immune cells to identify and protect human beta cells, essential for insulin production. These cells were introduced into mice transplanted with human islet cells to model type 1 diabetes treatment. The engineered cells successfully protected the beta cells, allowing them to survive and produce insulin, whereas unprotected transplanted cells were destroyed.

“This is a major step forward in developing targeted therapies for autoimmune conditions and organ transplants,” said Professor Matthias Hebrok, Director of the TUM Center for Organoid Systems (COS). “The ability to modulate immune responses locally opens doors to safer and more effective treatments.”

Expanding Applications

Beyond type 1 diabetes and organ transplantation, the technology holds promise for refining CAR T-cell therapies in cancer treatment. By ensuring that CAR T cells attack only tumor cells while sparing healthy tissues, the approach could significantly enhance therapeutic precision. Furthermore, the research contributes to the optimization of stem cell therapies, ensuring the long-term functionality of transplanted tissues.

A Vision for the Future

The findings align with ongoing research at TUM’s Center for Organoid Systems (COS), a cutting-edge facility focused on advancing organoid technology and stem cell research. COS’s interdisciplinary approach brings together medicine, engineering, and natural sciences to translate fundamental research into clinical applications.

Supported by funding from institutions including the National Institutes of Health and the Valhalla Foundation, this research exemplifies the potential of innovative immune regulation strategies to revolutionize treatments for complex diseases.

Publication Reference

Nishith R. Reddy, Hasna Maachi, Yini Xiao, et al., “Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs,” Science (December 2024). DOI: 10.1126/science.adl4793

For more information, visit the TUM Center for Organoid Systems (COS) and the Munich Institute of Biomedical Engineering (MIBE), where this groundbreaking work continues to bridge research and clinical practice.

Further information and links

• Prof. Matthias Hebrok is Director of the new TUM Center for Organoidsystems (COS). Organoid research is a key research area at TUM. With the construction of the TUM Center for Organoid Systems (COS) at the Garching Research Center, TUM is developing a facility unlike any in Europe. It will utilize TUM’s status as a technical university with its own university clinic to transfer this ultramodern technology into medical-clinical applications.
• Prof. Matthias Hebrok conducts research at the Munich Institute of Biomedical Engineering (MIBE), an Integrative Research Institute at TUM. At MIBE, researchers specializing in medicine, the natural sciences, engineering, and computer science join forces to develop new methods for preventing, diagnosing or treating diseases. The activities cover the entire development process – from the study of basic scientific principles through to their application in new medical devices, medicines and software.
• The professorship of Applied Stem Cell and Organoid Systems is part of the TUM School of Medicine and Health.
• The project was funded by: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Valhalla Foundation

Media Contact:

Corporate Communications Center
Carolin Lerch
presse@tum.de

Prof. Dr. Matthias Hebrok
Technical University of Munich
Professorship of Applied Stem Cell and Organoid Systems
matthias.hebrok@tum.de

SOURCE: Technical University of Munich