Five people with severe autoimmune diseases have become the first to receive a world-leading treatment that uses genetically modified cells to drive the disease to a cure.
The four women and one man, ages 18 to 24, received modified immune cell transfusions to treat severe lupus, an autoimmune disease that can cause life-threatening damage to the heart, lungs, brain and kidneys.
The treatment pushed the disease to remission in all five patients, who had stopped taking their lupus treatment for between three and 17 months. Doctors say the apparent success raises hopes for treating other autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.
Lupus, or systemic lupus erythematosus, develops when the immune system mistakenly attacks healthy tissues and organs. The causes aren’t well understood, but researchers believe they may be caused by a viral infection, certain medications, and changes in the body around puberty and menopause.
The condition affects about 1 in 1,000 people, and it affects women much more than men. Diagnosis is difficult because the symptoms often flare up, stabilize and overlap with those of many other diseases. While lupus is mild in many people, it can cause extreme fatigue, organ damage, and joint pain.
Doctors in Germany treated five critically ill patients with CAR T cell therapy after other treatments failed to improve their symptoms. This approach has proven successful in fighting some types of cancer since it was first used in a leukemia patient in 2015. CAR T-cell therapy involves collecting the patient’s T cells – a key component of the immune system – and modifying them so that they attack the new. Targets, such as cancer cells, when re-infused into the body.
In the most recent work, doctors took T cells from patients with lupus and modified them so that, upon reinfusion, they attacked the patients’ B cells. In lupus, B cells produce autoantibodies, which attack healthy tissue rather than defending the body against invading pathogens.
According to the study in Nature Medicine, the treatment virtually eliminated patients’ abnormal B cells and significantly improved their condition. The disease affected multiple organs in all five patients, but after treatment severe symptoms including arthritis, fatigue, cirrhosis of the heart valves, and pneumonia disappeared.
Blood tests on the patients showed that their B cells had recovered after about four months of treatment, but that they were no longer producing abnormal antibodies and the patients remained disease-free. The authors wrote in the journal that the treatment led to a “reboot of the immune system.”
“We are very excited about these results,” said Professor Georg Schett, a rheumatologist who led the work at the Friedrich-Alexander University in Erlangen-Nuremberg. Many other autoimmune diseases that depend on B cells and show autoantibodies may respond to this treatment. These include rheumatoid arthritis, polymyositis, and systemic sclerosis. But also diseases such as multiple sclerosis may be highly responsive to CAR T-cell therapy.”
Schett’s team was careful to make sure the treatment didn’t weaken patients’ immune systems and leave them more susceptible to infections. To test this, they evaluated patients’ responses to multiple vaccines, including measles, rubella, mumps, hepatitis B, tetanus and diphtheria, before and after treatment. The patients’ immune responses were not substantially different after treatment, indicating that they mainly targeted stray cells that make antibodies.
“This is an excellent study that promises to extend CAR T cell therapy, which has so far seen its main effect in treating blood cancers, to autoimmune diseases such as lupus that are not well controlled in some patients with other drugs,” said Dr. He studies immune system regulation in inflammation and cancer at the University of Cambridge.“I am very excited about the prospects for this type of live therapy in indications beyond cancer.” – Guardian