Scientists might have uncovered a potential cure for diabetes and other debilitating autoimmune diseases, as highlighted in a new study. Researchers from NYU Langone Health, the Chinese Academy of Sciences, and Zhejiang University investigated the reasons behind the immune system’s malfunction, which causes it to attack the body, leading to various chronic conditions.
This research focused on autoimmune disorders like type 1 diabetes, multiple sclerosis (MS)—a serious neurological illness—and hepatitis, which results in liver inflammation and damage. Together, these conditions impact over 10 million Americans. Although treatments exist that manage symptoms to some extent, they can also lead to lasting harm and, in some cases, premature death.
Many patients are often prescribed a lifelong regimen of intensive medications that can alleviate symptoms, but come with side effects such as swelling, weight gain, and osteoporosis. The promising new treatment investigated, called LAG-3/TCR Bispecific T Cell Silencer or BiTS, claims to have the ability to halt these relentless diseases by ‘resetting’ the immune system, refraining it from attacking healthy tissues.
Experts predict this could represent one of the most significant treatment advancements in many years.
T-cells, a type of white blood cell essential for the immune system, constantly patrol the body to identify and eliminate harmful cells and organisms. Unfortunately, they sometimes struggle to tell the difference between healthy and diseased cells, often leading to the accidental attack of healthy tissue.
Research indicates that by introducing a protein known as chimeric antigen receptor (CAR), T-cells can have their DNA altered, changing how they respond to various cells in the body. Once these T-cells transform into CAR T-cells, they are replicated in a lab and reintroduced into the patient’s body weeks later.
However, manipulating T-cells can be tricky because suppressing their function may weaken the immune system, raising vulnerability to infections and cancers. CAR T-cell therapy also carries risks of severe effects on the nervous system, a condition known as immune effector cell-associated neurotoxicity syndrome (ICANS), which can trigger headaches, confusion, agitation, seizures, and speech difficulties.
The recent study in mice, published in the journal Cell, suggests that a newly-designed antibody might effectively control T-cells without causing these adverse effects. The findings emphasize the role of T-cell receptors (TCRs) and checkpoints in autoimmune diseases. TCRs, activated by the body’s own proteins, often escalate autoimmune responses. Checkpoints like LAG-3, when engaged with specific partners, can inhibit T-cell activity, reducing their ability to attack malignant cells.
Introducing the antibody can help prevent T-cells from damaging healthy tissue while still regulating their functions and supporting the immune system. This strategy is being examined as a treatment option for various autoimmune disorders.
In models of autoimmune hepatitis, the BiTS treatment managed to decrease T-cell infiltration and liver damage. Moreover, in mice predisposed to multiple sclerosis, a preventive dose of BiTS administered before symptoms appeared showed a significant reduction in disease progression.
“Our study may inspire therapeutically innovative designs like BiTS for other diseases,” noted co-first author Jia You from Dr. Wang’s lab. Dr. Jun Wang, co-senior author and assistant professor at NYU Grossman School of Medicine, stated, “These findings unveil a complex mechanism for treating T-cell-driven autoimmune conditions, which currently lack effective immunotherapies.”
