Scientists are calling the results are “spectacular” and “incredibly exciting,” saying the findings may herald a new era of managing autoimmune diseases that, like cancer, are notoriously difficult to treat.
Lupus is a lifelong disease that, in the worst cases, causes organ damage in addition to disabling joint pain and affects about 1 in 1,000 people, mostly women of childbearing age.
Like many other autoimmune diseases, the root causes of lupus remain an unclear mix of genetic and environmental factors.
Symptoms like inflammation are it is usually treated with courses of steroids and immunosuppressive drugs that subdue the disease-causing elements while failing to eliminate them.
That may change, however, if the promising results of a new study led by rheumatologist Georg Schett of the University of Erlangen-Nuremberg in Germany can be replicated to safely “reset” the immune systems of more lupus patients.
Inspired by the success of cell-based therapies called chimeric antigen receptor (CAR) T-cell therapies that have yielded surprising results in blood cancers, researchers have been methodically testing if the approach could also work for lupus – try therapy first in micethen to a patientand now four more.
CAR-T therapies work by harvesting a patient’s immune cells and engineering them to recognize and destroy rogue cells, whether cancer cells or other immune cells, when they are infused back into the body
In the case of this particular trial, the therapy was designed to hunt down hordes of defective B cells, specifically those adorned with a cell-surface protein called CD19 that in people with lupus pumps out autoantibodies that stick by mistake in the body’s own cells.
Following orders, the immune system rushes to attack these tissues, damaging organs and causing joint pain, fatigue and skin rashes.
Blood tests showed that the unique therapy eliminated the patients’ errant B cells without causing significant side effects, after which the disease-causing autoantibodies fell below detectable levels. The patients’ symptoms also improved so much that months later, they no longer needed to take the medications they once did to control their condition.
Although it is too early to say whether patients are cured and too early to say what fraction of lupus patients would respond to treatment, the findings are encouraging.
The five patients (four women and one man) have been in remission for 5 to 17 months, and in that time, their disease has not relapsed despite the resurgence of B cells a few months after treatment.
Crucially, these newly made B cells have not produced the autoantibodies that their dysfunctional predecessors did, so the researchers suspect that they have actually managed to reset the patients’ immune systems, although only time will tell.
“We were very surprised at how effective it was,” Schett told STAT News reporter Isabella Cueto. “I have to say it blew us away.”
Immune system function was also not completely suppressed. Rather, the therapy selectively hunted down antibody-producing B cells while preserving immunity to chickenpox, measles, mumps, and rubella, diseases against which patients had previously been vaccinated.
“This would seem to be the holy grail of treatment,” Mark Leick, a medical oncologist at Massachusetts General Hospital who was not involved in the trial, told STAT News.
Of course, the therapy will need to be tested in larger groups of lupus patients to see if remission lasts and if it works for some, all, or most patients. Researchers will also need to continue to monitor the known side effects of CAR-T therapy, which in some blood cancer patients can trigger systemic inflammation.
Schett’s team is already planning another trial to test whether other autoimmune diseases, such as rheumatoid arthritis and scleroderma, may also respond to CAR-T therapy. For several years, scientists have speculated that this might be possible, and now it seems like a real possibility.
Another obstacle to deploying the therapy, however, if it proves safe and effective for treating lupus or other autoimmune diseases, is cost.
Because CAR-T therapies are tailored to each patient and manufacturing modified immune cells requires special manufacturing capabilities, it might only be feasible to use CAR-T therapies as a last resort for lupus patients with severe disease that do not respond to other drugs. .
The study was published in Natural Medicine.