Scientists Reprogram Immune Cells to Stop Autoimmune Attacks

A revolutionary approach to immune therapy has emerged: engineered immune cells that protect healthy tissue without compromising the body’s defenses. This could transform treatments for diabetes, transplants, and cancer.

When the immune system becomes unbalanced, it can lead to serious problems, such as type 1 diabetes, other autoimmune diseases, or organ rejection after a transplant. Current treatments often involve suppressing the entire immune system, which can cause severe side effects, including a higher risk of infections and other complications. A better approach would be to regulate the immune response in a precise and targeted way. That’s exactly what researchers have now achieved by engineering specialized immune cells designed to restore balance without compromising overall immunity.

Engineering Immune Cells to Protect Rather Than Attack

The immune system defends the body against viruses, bacteria, and other threats by identifying harmful invaders and mounting a response. It also distinguishes between the body’s own cells and foreign ones, adjusting its reaction as needed. However, when the immune system becomes dysregulated, it can mistakenly attack the body’s own tissues. This happens in conditions like type 1 diabetes, where the immune system destroys insulin-producing beta cells in the pancreas. It can also reject transplanted organs, treating them as foreign threats. While immunosuppressant drugs can prevent these harmful reactions, they come with serious risks, including increased vulnerability to infections and cancer.

Now, researchers have developed specialized immune cells designed to regulate and calm excessive immune responses. These engineered cells recognize and protect healthy tissues by preventing T-killer cells from attacking them. This breakthrough could help stop organ rejection and reduce the need for strong immunosuppressant drugs, offering a safer and more targeted approach to immune regulation.

A Collaborative Effort in Cutting-Edge Science

The work was carried out at UC San Francisco (UCSF) with significant contributions from Matthias Hebrok, Professor of Applied Stem Cell and Organoid Systems at the Technical University of Munich (TUM), and Dr. Hasna Maachi, postdoctoral researcher at TUM and Helmholtz Munich. The study was published in the journal Science.

“This technology can put the immune system back into balance,” said Wendell Lim, PhD, UCSF professor of cellular and molecular pharmacology. “We see it as a potential platform for tackling all kinds of immune dysfunction.”

Reprogramming Immune Cells for Targeted Protection

To engineer the regulatory immune cells, the researchers are using the same type of cells as in CAR T-cell immunotherapies. For the latter, they are specifically engineered to target tumor cells. By contrast, the engineered regulatory immune cells are designed to protect healthy cells. The produce a combination of proteins that the researchers have found to be particularly effective for regulation: one has an anti-inflammatory effect, while the other scavenges pro-inflammatory substances. The cell system can be flexibly adapted for different applications.

The Goal: Safeguarding Beta Cells in Diabetes

To test the application in type 1 diabetes, the researchers modified the cells to recognize and protect human beta cells. They introduced the engineered immune cells into mice that had received a transplant of human islet cells, modeling the treatment for type 1 diabetes. The experiments were successful: The transplanted beta cells that were protected by the engineered cells survived and continued to produce insulin. In contrast, transplanted cells without the protective engineered T cells were destroyed.

A Future of Precision Immune Therapies

The authors envision a future in which organ transplant patients, or those with autoimmune diseases, receive therapies that only treat the specific regions of the body where the immune system is misbehaving, instead of shutting down the whole system. The new technology also could be used to finetune CAR T cell therapies for cancer, so these CAR T cells only attack tumors, and not healthy tissue.

Being able to modulate immune responses and to further optimize functional properties of stem cell derived tissues is central to developing long-lasting stem cell therapies, a clear goal for organoid researchers at the new Center for Organoid Systems (COS) at TUM.

Reference: “Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs” by Nishith R. Reddy, Hasna Maachi, Yini Xiao, Milos S. Simic, Wei Yu, Yurie Tonai, Daniela A. Cabanillas, Ella Serrano-Wu, Philip T. Pauerstein, Whitney Tamaki, Greg M. Allen, Audrey V. Parent, Matthias Hebrok and Wendell A. Lim, 6 December 2024, Science.
DOI: 10.1126/science.adl4793

The project was funded by: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Valhalla Foundation

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