Scientists use lupus patients’ cells to treat their autoimmune disease

German scientists report that they have used lupus patients’ own cells to treat this type of autoimmune disease successfully, according to a report published by Wired on Friday.

Treating lupus and other autoimmune disorders

Autoimmune diseases happen when the body's natural defense system can't tell the difference between its own cells and foreign ones, causing it to attack normal cells and create havoc.

Today, there are more than 80 types of autoimmune diseases that affect a wide range of body parts, and all are debilitating and devastating. This is why the new treatment offers so much promise.

“This is as close to a cure as I can see,” Hoang Nguyen, senior scientific program manager at the Lupus Research Alliance, told Wired.

“They corrected the cells that produce antibodies against the body’s own tissues,” added Nguyen, who wasn’t involved in the study.

The study was published on September 15 in the journal Nature Medicine.

Before we get too excited, it should be noted that however efficient the treatment was (all participants ended up in full remission) it was only conducted on a very small sample of five people.

The treatment is called CAR-T therapy, and it has been previously used against some cancers. It involves modifying a patient’s T cells, a part of the immune system that focuses on specific foreign particles, and triggering them into seeking out and destroying a specific target in the body.

What is the target? The notorious B cells, a part of the immune system that focuses on specific foreign particles and develops self-attacking autoantibodies in people with lupus.

For this particular treatment, doctors took T cells from patients and genetically engineered them to have the capacity to identify a protein called CD19 that appears on the surface of B cells.

They then infused these new T cells back into the patients and let them run loose to find and eliminate faulty B cells.

Impressive results

The results were nothing short of impressive. It took about 100 days for the patients to start making new healthy B cells while the autoantibodies completely disappeared. All participants in the trial have now been symptom-free from five to 17 months, the longest follow-up period so far.

The researchers are now hoping that the patients will not relapse. CAR-T therapy has shown 40 to 50 percent relapse chances in those treated for cancer, so the fear that the lupus might return remains high.

However, there are some characteristics of autoimmune diseases that make them a better fit for treatment with CAR-T.

“The difference between cancer and autoimmunity is that in cancer, there are usually more cells involved,” told Wired Georg Schett, vice president of research at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

“Whereas in autoimmunity, the number of B cells is much lower, and therefore it seems that the safety profile of CAR-T cell therapy and autoimmunity is much better than in cancer.”

Could this be the cure that will forever change autoimmune disorders?

Abstract:

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease characterized by adaptive immune system activation, formation of double-stranded DNA autoantibodies and organ inflammation. Five patients with SLE (four women and one man) with a median (range) age of 22 (6) years, median (range) disease duration of 4 (8) years and active disease (median (range) SLE disease activity index Systemic Lupus Erythematosus Disease Activity Index: 16 (8)) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use chimeric antigen receptor (CAR) T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti-CD19 CAR vector, expanded and reinfused at a dose of 1 × 106 CAR T cells per kg body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. CAR T cells expanded in vivo, led to deep depletion of B cells, improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies. Remission of SLE according to DORIS criteria was achieved in all five patients after 3 months and the median (range) Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (2). Drug-free remission was maintained during longer follow-up (median (range) of 8 (12) months after CAR T cell administration) and even after the reappearance of B cells, which was observed after a mean (±s.d.) of 110 ± 32 d after CAR T cell treatment. Reappearing B cells were naïve and showed non-class-switched B cell receptors. CAR T cell treatment was well tolerated with only mild cytokine-release syndrome. These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE.