Five critically ill lupus patients saw their disease go into remission after a single infusion of modified immune cells, in a small trial that borrows from cancer therapy to harness patients’ own cells to treat the autoimmune disease .
Scientists are call the “dramatic” and “incredibly exciting” results, saying the findings could herald a new era in the management of autoimmune diseases which, like cancer, are notoriously difficult to treat.
Lupus is a chronic disease that, at worst, causes organ damage in addition to debilitating joint pain and affects approximately 1 in 1,000 people, mostly women of childbearing age.
Like many other autoimmune diseases, the root causes of lupus remain an uncertain mix of genetic and environmental factors.
Symptoms such as inflammation are usually treated with courses of steroids and immunosuppressive drugs that subdue pathogens without eliminating them.
That could 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 system of a larger number of patients with lupus.
Inspired by the success of cell therapies called chimeric antigen receptor (CAR) T-cell therapies that have shown astonishing results in blood cancers, researchers methodically tested whether the approach could also work for lupus – test the therapy first In micethen in an illnessand now four more.
CAR-T therapies work by harvesting a patient’s immune cells and engineering them to recognize and destroy unwanted cells, whether cancer cells or other immune cells, when injected 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 which, in people with lupus, pumps out autoantibodies that mistakenly lock onto the body’s own cells.
Following commands, the immune system rushes to attack these tissues, damaging organs and causing joint pain, fatigue and rashes.
Blood tests showed that the single therapy eliminated the patients’ misguided B cells without causing significant side effects, after which the pathogenic autoantibodies fell below detectable levels. The patients’ symptoms also improved so much that months later they no longer needed to take the medications they had previously taken to manage their condition.
Although it is too early to tell if patients are cured and too soon to tell what fraction of lupus patients would respond to treatment, the results are encouraging.
The five patients (four women and one man) have been in remission for 5 to 17 months, and during this time their disease has not relapsed despite a resurgence of B lymphocytes a few months after treatment.
Crucially, these newly made B cells failed to produce the autoantibodies of their dysfunctional predecessors, so the researchers suspect they did indeed succeed in rebooting patients’ immune systems – although time will tell.
“We were really surprised at how effective it was,” Schett told STAT News reporter Isabella Cueto. “I have to say it blew our minds.”
Immune system function was not nullified entirely either. Rather, the therapy selectively drove out antibody-producing B cells while preserving immunity against chickenpox, measles, mumps and rubella, diseases against which patients had previously been vaccinated.
“It seems 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 on 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 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 can also respond to CAR-T therapy. For several years scientists have speculated that it might be possible, and now it seems like a real possibility.
Another barrier to rolling out the therapy, if it proves safe and effective in treating lupus or other autoimmune diseases, is cost.
Since CAR-T therapies are tailored to each patient and manufacturing the modified immune cells requires special manufacturing capabilities, it may only be possible to use CAR-T therapies as a last resort to SLE patients with severe disease who do not respond to other medications. .
The study was published in Natural medicine.