Scientists welcome breakthrough in autoimmune disease therapy

Five people with severe autoimmune diseases have become the first in the world to receive a breakthrough therapy that uses genetically altered cells to drive the disease into remission.

The four women and one man, aged 18 to 24, received transfusions of modified immune cells to treat severe lupus, an autoimmune disease that can cause fatal damage to the heart, lungs, brain and kidneys.

The treatment led to disease remission in all five patients, who have now been off lupus medication for between three and 17 months. Doctors say the apparent success raises hopes for tackling other autoimmune conditions 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 are not well understood, but researchers believe it can be caused by viral infections, particular medications, and changes in the body around puberty and menopause.

The disease affects approximately one in 1,000 people and many more women than men. It is difficult to diagnose because symptoms often wax and wane, and overlap with those of several other illnesses. Although mild in many people, lupus can cause extreme fatigue, organ damage, and joint and muscle pain. One of the most common signs is a distinctive rash on the nose and cheeks.

Doctors in Germany treated five seriously ill patients with CAR T-cell therapy after other treatments failed to improve their symptoms. The approach has been successful in fighting certain cancers since it was first used in a leukemia patient in 2015. CAR T cell therapy involves harvesting the patient’s T cells, a key component of the system immune system, and modify them so that they attack new targets, such as cancer cells, when they are introduced back into the body.

In the latest work, doctors took T cells from lupus patients and modified them so that, when reinfused, they attacked the patients’ B cells. In lupus, B cells produce autoantibodies, which instead of defending the body against invading pathogens, attack healthy tissues.

According to the Nature Medicine study, the therapy eliminated the patients’ aberrant B cells and dramatically improved their condition. The disease affected multiple organs in all five patients, but after therapy severe symptoms such as arthritis, fatigue, fibrosis of the heart valves and lung inflammation cleared up.

Blood tests on the patients showed that their B cells recovered about four months after treatment, but they no longer produced aberrant antibodies, and the patients remained disease-free. Writing in the journal, the authors speculate that the therapy led to an “immune system reset.”

“We are very excited about these results,” said Professor Georg Schett, a rheumatologist who led the work at the Friedrich-Alexander University of Erlangen-Nuremberg. “Several other autoimmune diseases that depend on B cells and show autoantibodies can respond to this treatment. These include rheumatoid arthritis, myositis and systemic sclerosis. But also diseases like multiple sclerosis can be very sensitive to CAR T-cell treatment”.

Schett’s team was keen to make sure the therapy didn’t harm patients’ immune systems and leave them at greater risk of infection. To test this, they evaluated patients’ responses to multiple vaccines, including measles, rubella, mumps, hepatitis B, tetanus and diphtheria, before and after therapy. The patients’ immune responses were not substantially different after the treatment, suggesting that it primarily targeted wayward cells producing autoantibodies.

“This is an excellent study that promises to extend the reach of CAR T-cell therapy, which has so far seen its greatest impact in the treatment of blood cancers, to autoimmune diseases such as lupus that in some patients are poorly controlled with other drugs,” said Dr. Rahul Roychoudhuri, who studies immune system regulation in inflammation and cancer at the University of Cambridge. “I am very excited about the prospects for this form of living therapy in indications beyond cancer.”

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