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Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the Charité University Hospital in Berlin, Germany, have engineered a new type of specialized T cell that can be used to treat autoimmune encephalitis.
Autoimmune encephalitis is a condition in which the body’s own antibodies cross the blood-brain barrier and attack the brain. This triggers inflammation, leading to symptoms like memory loss, impairment of consciousness, seizures, and psychosis. The condition often requires treatment in the intensive care unit and can be fatal.
Although the exact cause of autoimmune encephalitis is unknown, scientists believe that benign and malignant tumors, as well as viral infections, like COVID-19, can trigger it. Research has shown that the prevalence of autoimmune encephalitis is similar to that of infectious encephalitis.
Autoimmune encephalitis is difficult to treat and current treatment often requires escalated immunotherapy that can affect the entire immune system. This can be problematic, especially for cancer patients.
“Instead of suppressing the entire immune system and eliminating not only the misdirected antibodies but also the more than 99% of beneficial antibodies, as we have done in the past, we set out to find a targeted approach,” said Harald Prüss, a professor at the DZNE and Charité and a corresponding author on the study published in Cell, in a press release.
In their preclinical study titled, “Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells,” the researchers focused on the most prevalent form of autoimmune encephalitis, NMDAR encephalitis. Commonly found in the central nervous system, NMDAR is a receptor that plays an important role in memory and learning. In NMDAR encephalitis, anti-NMDAR autoantibodies prevent the receptor from functioning properly.
To develop a targeted treatment for NMDAR encephalitis, the researchers extracted T cells from the blood of patients and genetically modified them. The resulting chimeric autoantibody receptor (CAAR) T cells are programmed so they can precisely identify and target the cells that produce anti-NMDAR autoantibodies, without affecting “healthy” immune cells around them.
“The surface of these cells is shaped in such a way that the CAAR T cells precisely dock onto them and kill them,” explained Momsen Reincke, a researcher at DZNE and Charité and one of the study’s primary authors.
Currently, scientists believe that once targeted, these cells cannot reproduce and are therefore unable to produce more harmful anti-NMDAR autoantibodies.
As a next step, the DAZN and Charité researchers want to organize a clinical trial to test their therapy in humans. To start with, they will develop one targeted therapy per NMDAR encephalitis patient but hope to develop an off-the-shelf treatment in the future.
“Given the rapid developments in the field of cell therapies… the next step could presumably be to use cells with which treatment no longer has to be patient-specific. That would be far less costly,” concluded Prüss.
