Systemic lupus erythematosus (SLE) is a serious autoimmune disease with an incidence of 0.1% in the general population, mainly affecting young women. In this lifelong disease, the immune tolerance of nuclear antigens, including double-stranded DNA (dsDNA) and nuclear protein, leads to T lymphocytes, inhibitory T cell function, B cell hyperplasia, resulting in a large number of autoantibodies against dsDNA and other nuclear antigens, then in a series of different organs triggered immune complex induced inflammatory response, mainly affecting the joints and skin, and may lead to serious damage to organs.

 Recent years have seen significant advances in the treatment of systemic lupus erythematosus, however, some patients still do not respond to current therapies and thus are at high risk of organ failure and even death. Moreover, there is no reliable strategy to alleviate or even cure the disease without medication, therefore, patients usually require lifelong treatment.

In August 2021, researchers from the University of Erlangen-Nuremberg in Germany published a paper in the New England Journal of Medicine (NEJM) [1] on CAR-T cell therapy in a 20-year-old woman with severe systemic lupus erythematosus, which quickly alleviated her condition without significant side effects. It is also the first CAR T cell therapy to treat systemic lupus erythematosus. Since then, the team has successfully treated dozens of patients with multiple autoimmune diseases, including systemic lupus erythematosus, by using CAR-T cell therapy.

 Recently, the team published a paper titled: CART-cell therapy rescues adolescent with rapidly progressive lupus nephritis from haemodialysis

In fall 2022, this one was called Uresa A. The girl developed migraine, fatigue, joint and muscle pain, a typical erythema butterfly rash on her face, accompanied by a high fever. After the age of age, she was diagnosed with a severe autoimmune disease —— systemic lupus erythematosus (SLE), the condition continued to worsen, has seriously affected her ability to live a normal life.

 Next, the Uresa A. She was treated with a variety of drugs, but they affected her liver and continued to deteriorate, and her kidney function deteriorated rapidly, and more than 50% of patients with systemic lupus erythematosus developed a kidney disease called lupus nephritis. By this point, her kidneys were unable to expel the fluid, causing severe water retention, causing swelling in her legs, hands, feet and face, and high blood pressure. The treatment team tried to use chemotherapy to suppress her overactive immune system to improve her kidney deterioration, but it did not improve, her kidney eventually failed and she did not start dialysis treatment.

 CAR T cell therapy has been widely used to treat patients with blood cancers such as leukemia or lymphoma, as well as some adult patients with severe autoimmune diseases, and has never been used in children with autoimmune diseases.

But at this time, Uresa A. Facing a situation that all the available drugs had been used, but her systemic lupus erythematosus was still progressing rapidly, the treatment team decided to try the last resort —— CAR-T cell therapy.

Patient Uresa A.(Front row, middle) and her treatment team

 The treatment team quickly completed the preparatory work and started targeting the Uresa A. The CAR-T cell therapy, Uresa A. She first received mild chemotherapy, leaving some room for the CAR T cells in her bone marrow. On June 26,2023, at age 15, Uresa A. She received an infusion of CAR T cells specifically modified for her, and she became the world's first child with an autoimmune disease to receive CAR T cell therapy. These quick actions ensured that lupus had not yet caused permanent damage to any of her organs.

 From the third week after treatment, her kidney and lupus markers improved and all symptoms gradually disappeared, which the treatment team said had never had any effect before. At the end of July 2023, only one month after CAR-T cell therapy, Uresa A. Already to go home and start a normal life.

The treatment team stated that, after the treatment, the Uresa A. Large numbers of CAR T cells remain in the blood, and these CAR T cells eliminate not only harmful B cells but also healthy B cells, meaning that her body may not be able to properly defend against certain infections. Therefore, before her own B cells recover, it is necessary to return to the hospital to receive intravenous immunoglobulin once every 4 weeks to boost immunity.

 Now, a year later, the Uresa A. Said: A year after the treatment, I feel as good as before the diagnosis, except for the occasional cold.

In addition to the once-monthly intravenous immunoglobulin, Uresa A. She no longer needed any medication or dialysis, and she was once seriously ill and had kidney failure, but now her symptoms are gone and her kidneys have fully recovered. The research team is planning clinical trials of CAR-T cell therapy in other children and adolescents with autoimmune diseases.

Paper link:

1. https://www.nejm.org/doi/full/10.1056/NEJMc2107725

2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00424-0/fulltext