Researchers have engineered a protein that selectively shuts down immune cells responsible for autoimmune diseases, such as Type 1 diabetes and multiple sclerosis, without broadly weakening the body’s defenses against infections and cancer. The study, published in Cell, demonstrates how holding two specific protein complexes together on T cells can eliminate autoimmune tissue damage while preserving normal immune function.
The approach addresses a longstanding challenge in treating autoimmune diseases, where T cells mistakenly attack the body’s own tissues instead of foreign invaders. Current treatments often suppress the entire immune system, creating dangerous vulnerabilities to infections and malignancies.
The research team discovered that spatial relationships between proteins on T cell surfaces are crucial for controlling immune responses. They found that when a protein called LAG-3 comes close to a T cell receptor, it can effectively dial down T cell activity by disrupting key activation signals.
Engineers created a “bispecific” antibody that forces these proteins to stay close together, dramatically enhancing LAG-3’s ability to suppress overactive T cells. The engineered antibody, called BiTS, proved effective in reducing inflammatory damage in Type 1 diabetes models and decreasing liver damage in autoimmune hepatitis. It also prevented disease symptoms in multiple sclerosis models when given preventively.
The approach leverages a unique feature of LAG-3 compared to other immune checkpoints. While it is less potent than PD-1 checkpoints used in cancer therapy, its spatial requirements make it ideal for targeted suppression without completely shutting down immune surveillance.
This breakthrough represents a significant advance in treating autoimmune diseases, where over 50 million Americans are affected. The researchers have formed a startup company to commercialize their findings, suggesting confidence in translating this laboratory discovery into clinical applications that could benefit patients facing these challenging conditions.
Source: https://scienceblog.com/scientists-design-protein-that-silences-rogue-immune-cells