Cell-Killing Cancer Therapy Treats Lupus Successfully

In a first-of-its-kind clinical trial, researchers in Germany used a cancer-killing cell therapy to successfully treat lupus in a small number of patients.

Their study, published online September 15 in Nature Medicine, included five patients with systemic lupus erythematosus (SLE). All of the patients were treated with genetically engineered T cells known as chimeric antigen receptor (CAR) T-cell therapy, a treatment regularly used to kill cancer cells. Researchers harvested the patients’ immune cells and engineered them to destroy dysfunctional cells when infused back into the body.

The five patients — all of whom had an aggressive form of the autoimmune disease — underwent a single infusion of the experimental treatment. All five patients were able to stop their standard treatments for as long as 17 months following the therapy, the study found. The patients also stopped experiencing severe symptoms such as lung inflammation, fibrosis of the heart valves, arthritis, and fatigue. The patients have not relapsed.

“Our data reveal unexpected insights for a role of CAR T cells in nonmalignant diseases that could provide new opportunities for the treatment of autoimmune disease,” the study authors write.

Lupus is a chronic inflammatory disease in which the immune system attacks the body’s own cells. Both antibody-producing B and T cells in individuals with lupus become overactive, which can lead to a flare of symptoms that range from mild pain and fatigue to life-threatening inflammation and tissue damage. They are often treated with medications that deplete their B cells or change the way they function to help wipe out infected cells.

Dr Michael Belmont

The approach used by the study researchers is similar to monoclonal antibody therapies that destroy dysfunctional B cells, such as rituximab (Rituxan and biosimilars) and obinutuzumab (Gazyva), according to Michael Belmont, MD, co-director of New York University’s Lupus Center and medical director of Bellevue Hospital Lupus Clinic in New York City.

“Previously, this has been accomplished with monoclonal antibodies that target surface markers on B cells and results in their removal,” said Belmont, who was not connected to the study. “The report describes a novel approach that harnesses a patient’s own T cells, another type of white blood cell, to eliminate that patient’s own B cells.”

Preclinical studies involving mice previously showed that CAR T-cell therapy could help to reset the immune system. However, this latest study also found that patients did not need to continue any of their previous therapies, even after they regained their B cells about 4 months after the therapy.

Dr Mehrnaz Hojjati

“A deep depletion of CD19+ B cells and plasmablasts in the tissues could trigger an immune reset in SLE that could allow the cessation of immunosuppressive treatment,” said Mehrnaz Hojjati, MD, a rheumatologist and director of rheumatology operations at Loma Linda University Health in Loma Linda, California. Hojjati was not affiliated with the study.

While the single-treatment therapy is promising, transfused T cells do carry risks. Some of the patients in the study experienced fever and muscle pain following the procedure, the authors noted. Belmont said more serious risks for this kind of therapy may include organ injury.

“This treatment can [also] increase incidence, for example, of pneumonia or shingles,” he said.

The study authors initially documented their work in a correspondence published in August 2021 in The New England Journal of Medicine. At that time, they reported that a 20-year-old woman with a severe refractory SLE went into remission following the treatment.

The five patients in the current study — four women and one man — were aged 18-24 years. All of the patients had previously been treated with several immunosuppressive medications, the study authors noted.

“This is an exciting approach, but many more patients need to be treated to really understand the efficacy and safety,” Belmont said.

Experts, including Belmont, also said the procedure is also costly and requires access to labs that can engineer a patient’s own T cells after they’ve been donated.

“The entire process must maintain sterility to avoid contamination, which would be harmful when reinfused into the patient,” he said.

Dr Arthur Kavanuagh

According to Arthur Kavanaugh, MD, professor of medicine at UC San Diego Health, this form of therapy may be an option for severe refractory patients who have not responded well to other more established therapies.

“[It’s] exciting data, but very intense and so not likely to be something for an average patient in the near future,” said Kavanaugh, who was not affiliated with the study.

The study authors say they intend to create a larger trial to further explore which type of patient may benefit the most from this treatment, and for how long.

The study was supported by the German Research Foundation, the German Federal Ministry of Education and Research, the European Union, and the Innovative Medicines Initiative-funded project, Rheuma Tolerance for Cure.

The study received no commercial funding, and the authors said they had no competing interests related to the study. None of the experts interviewed reported relevant financial relationships.

Nat Med. Published online September 15, 2022. Abstract  

For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube, and LinkedIn

Source: Read Full Article