When the immune system is imbalanced, it can lead to serious problems such as type 1 diabetes, other autoimmune diseases, or rejection after an organ transplant. Current treatments typically suppress the entire immune system, which can lead to serious side effects, including an increased risk of infection and other complications. A better approach would be to modulate the immune response in a precise and targeted manner.That's exactly what researchers have now achieved, engineering specialized immune cells to restore balance without compromising overall immunity.
Engineering immune cells to protect rather than attack
The immune system protects against viruses, bacteria, and other threats by identifying and responding to harmful invaders. It also differentiates between the body's own cells and foreign cells and adjusts its response as needed. However, when the immune system is dysregulated, it mistakenly attacks the body's own tissues. In diseases like type 1 diabetes, the immune system destroys the insulin-producing beta cells in the pancreas. The immune system also rejects transplanted organs, viewing them as a foreign threat. While immunosuppressants can prevent these harmful reactions, they also carry serious risks, including an increased risk of infection and cancer.
Now, researchers have developed specialized immune cells designed to regulate and calm excessive immune responses. These modified cells recognize and protect healthy tissues, preventing T killer cells from attacking them. This breakthrough could help stop organ rejection, reduce the need for powerful immunosuppressants, and provide a safer, more targeted approach to immune regulation.
A cutting-edge scientific collaborative effort
This research was completed at the University of California, San Francisco (UCSF), with important contributions made by Matthias Hebrok, professor of applied stem cells and organoid systems at the Technical University of Munich (TUM), and Dr. Hasna Maachi, a postdoctoral researcher at the Technical University of Munich and Helmholtz University Munich. The study was published in the journal Science.
"This technology can bring the immune system back into balance," said Dr. Wendell Lim, professor of cellular and molecular pharmacology at the University of California, San Francisco. "We see it as a potential platform to address various immune dysfunctions."
Reprogram immune cells for targeted protection
To engineer regulatory immune cells, the researchers used the same types of cells used in CART cellular immunotherapy. In the case of the latter, they are specifically designed to target tumor cells. In contrast, engineered regulatory immune cells are designed to protect healthy cells. They produce a combination of regulatory proteins that researchers found to be particularly effective: one protein that is anti-inflammatory and another that clears out pro-inflammatory substances. This cell system can be flexibly adapted to different applications.
Goal: Protect beta cells in patients with diabetes
To test the cells' use in type 1 diabetes, the researchers engineered the cells to recognize and protect human beta cells. They introduced the modified immune cells into mice that had received human islet cell transplants to simulate the treatment of type 1 diabetes. The experiment was a success: The transplanted beta cells, protected by the engineered cells, survived and continued to produce insulin. In contrast, transplanted cells without the protection of engineered T cells were destroyed.
The future of precision immunotherapy
The authors envision a future in which organ transplant patients or patients with autoimmune diseases receive therapies that only treat specific areas of the body where the immune system is abnormal, rather than shutting down the entire system. The new technology could also be used to fine-tune CART cell therapies used to treat cancer so that the cells attack only tumors and not healthy tissue.
The ability to modulate immune responses and further optimize the functional properties of stem cell-derived tissues is central to the development of long-lasting stem cell therapies and is a clear goal for organoid researchers at the newly established Center for Organoid Systems (COS) at the Technical University of Munich in Germany.
Compiled from /ScitechDaily