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Five lupus patients in remission after CAR T-cell therapy

Written by Lauren Robertson, Science Writer

Research published on September 15th in Nature Medicine has provided new evidence for the use of chimeric antigen receptor (CAR) T-cell therapy in autoimmune diseases.

The study, led by rheumatologist Georg Schett, looked at the effect of CAR T-cell therapy on five lupus patients. Incredibly, they found that treatment managed to push the patients into remission, acting almost as a “reboot” for the immune system.

The lupus dilemma

Systemic lupus erythematosus is an autoimmune condition caused by the adaptive immune system forming autoantibodies that target the body’s healthy cells. The condition affects more than 1.5 million people in the US alone and there is currently no known cure, meaning patients often require lifelong treatment to keep symptoms under control.

Scientists are still unsure about the causes for this disease, but the consensus is that viral infection, particular medicines, or simply natural changes in the body (such as menopause) trigger the immune system to mistakenly attack healthy cells.

Usually used to treat cancer, CAR T therapy (or T-cell transfer therapy) is a specialised immunotherapy where changes are made to a patient’s T cells to increase their efficiency in recognising and destroying cancer. These modified T cells are then put back into the body via an intravenous drip. Six therapies have been approved by the FDA, mostly covering certain blood cancers.

Previous studies have hinted at the potential for using CAR T-cells to treat lupus and other autoimmune diseases, so Schett’s team decided to take the idea one step further.

A new era for CAR T

Five people with severe lupus involving multiple organs who hadn’t responded to standard therapy were selected to receive the novel treatment – the group comprised four women and one man, all aged 18-24. When used in cancers, CAR T cells are targeted to the CD20 B lymphocyte antigen. In the case of lupus, the cells were trained to target CD19.

Just three months after treatment, drastic improvements were seen – including a remission of organ involvement and the disappearance of disease-related autoantibodies. Severe symptoms such as arthritis, fatigue, fibrosis of the heart valves, and lung inflammation all cleared up after treatment.

Incredibly, the patients needed no additional medications and (at the time the study was published) had been off lupus medication for between 3 and 17 months. One of the most important findings of this study is simply that the use of CAR T cells appears to be safe for patients with autoimmune diseases. Compared to some cancer studies, where this therapy type has caused side effects such as cytokine release syndrome and trouble breathing, the side effects seen here were mild.

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

An important follow up to these results was to test whether the immune system was still properly functioning after treatment. To do this, the team injected the patients with multiple vaccines and observed their response. Thankfully, the immune responses were not much different after treatment. In fact, it appears that the B cell populations had recovered about 4 months post-treatment, but they were naïve B cells and showed non-class-switched receptors – in other words, they no longer produced the aberrant antibodies. The authors speculate the treatment caused an immune system “reboot”.

Hope for the future

Future work will focus on deciphering whether the immune system has undergone a permanent change and behaves normally moving forward. “Longer monitoring of patients will be important to test whether they enjoy long-term disease-free remission and are eventually cured from [lupus],” Schett said.

The findings are certainly exciting and offer hope for those suffering from an autoimmune disease with no current cure.

There’s no doubt this will get widespread coverage in the coming weeks, but there’s also a need to proceed with caution. The results are exciting, but a larger study now needs to be conducted to confirm the findings.