CD19-targeted CAR T-cell therapy sparks rapid remission in lupus patient

Reuters Health - 05/08/2021 -  Doctors in Germany say they have produced a rapid clinical remission in a 20-year-old woman with severe systemic lupus erythematosus (SLE) using modified T cells that clear B cells from the blood.

"The patient has been without any symptoms for more than four months and could stop all the treatments. Arthritis, rash, pleurisy, proteinuria and fatigue are absent," coauthor Dr. Georg Schett of Friedrich-Alexander-University Erlangen-Nuremberg told Reuters Health by email.

"We see this as a treatment for severe cases," he said, reporting that "the entire disease fell apart after CAR T administration. We see this as a cure for the moment, but we have to wait longer to see if this effect is long-lasting."

The group is currently testing the therapy on two additional patients with SLE. The results from the first woman were published in the New England Journal of Medicine.

The technique uses autologous CD19 CAR T cells trained to get rid of the B cells that are creating antibodies that, in turn, are attacking the patient.

Those antibodies "are a hallmark of the disease," said Dr. Schett. "They come from B cells and form immune complexes with DNA from dying cells which trigger inflammation in the kidneys, heart, lungs, joints and the skin."

"Thus, getting rid of B cells is an important approach in SLE," he said.

The 20-year-old woman had not responded well to previous SLE therapy and had active lupus nephritis, pericarditis, pleurisy, rash, arthritis and nephrotic syndrome.

Three days after the infusion therapy, CAR T-cells represented 0.31% of all circulating T cells. By day 9, the level peaked at 28% and the cells persisted to some degree for the next seven weeks.

"Expansion of CAR T cells preceded the complete and sustained depletion of circulating B cells," the researchers report.

The level of double-stranded DNA autoantibodies plummeted, going from more than 5,000 U/mL and crashing to 4 U/mL over five weeks.

At the same time, proteinuria levels tanked and the patient's score on a lupus disease activity index went from 16 to zero.

Dr. Schett explained that because antibodies against DNA disappear, "their accumulation in the kidneys stops. This leads to cessation of inflammation and the filter function of the kidneys can recover (if the structure is still intact)."

"Before this patient, we did not know whether a deep and sustained depletion of B cells would have such a profound effect on SLE, but it obviously does," he said.

"One can live without B cells but one has to know that you do not mount an immune memory against new infections or vaccines in such cases," Dr. Schett explained. "However, this is acceptable given that uncontrolled SLE is a life-threatening condition."

It costs about $50,000 to manufacture the genetically modified cells, he said. By comparison, "commercial products used for lymphoma are much more expensive - around $300,000."

The researchers say the therapy might have a role in other diseases based on autoimmunity with autoantibodies, such as type-1 diabetes, multiple sclerosis or rheumatoid arthritis.

The study did not have commercial funding.

SOURCE: https://bit.ly/2V4wdwV The New England Journal of Medicine, online August 4, 2021

By Gene Emery



Posted on 5 August 202117 August 2021