Five patients with hard-to-treat lupus went into remission after scientists modified their immune cells using a technique normally used to treat cancer. After the single therapy, all five patients with autoimmune disease stopped their standard treatments and have not had a relapse.
This treatment, known as chimeric antigen receptor (CAR) T-cell therapy, needs to be tested in larger groups of lupus patients before it can be approved for widespread use. But if the results hold up in larger trials, the therapy could one day offer relief to people with moderate to severe lupus.
“For them, this is really a breakthrough,” said Dr. Georg Schett, director of rheumatology and immunology at the Friedrich Alexander University of Erlangen-Nuremberg in Germany. Schett is lead author of a new report describing the small trial, which was published Thursday (Sept. 15) in the journal Natural Medicine (opens in a new tab).
“It’s a single shot of CAR T cells and patients stop all treatments,” Schett told Live Science. “We were very surprised [at] how good is this effect.”
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Rebooting the immune system
Lupus is a chronic disease in which the immune system it inadvertently attacks the body’s own cells, causing inflammation, tissue damage, pain and fatigue. Symptoms, which range from mild to life-threatening, can appear in “flares” and patients often take multiple drugs to reduce their frequency and severity.
In lupus, dysfunctional B cells, a type of immune cell, pump “autoantibodies” that shine on the body’s cells and call out other cells to destroy them. Several drugs target these harmful B cells, but they don’t work for all lupus patients.
“There is a group that is really very severe and they go through multiple therapies and never go into remission,” Schett said.
Schett’s group theorized that these treatment-resistant lupus patients could potentially benefit from CAR T-cell therapy, which has previously been used to treat cancer patients During CAR T-cell therapy, doctors extract immune cells, called T cells, from a patient’s blood, genetically modify these T cells in the laboratory and inject them back into the patient’s body, according to the NIH National Cancer Institute (opens in a new tab) (NCI). In all approved cancer therapies, these engineered T cells target B cells with specific molecules on their surfaces, eliminating both problem cells and healthy B cells.
Without these B cells, patients may be more prone to infections, and CAR T-cell therapy also carries the risk of triggering “cytokine release syndrome,” in which T cells they suddenly trigger a flood of inflammatory molecules into the bloodstream. Therefore, despite its potential benefits, the treatment is not suitable for those with only mild disease.
For their trial, Schett and colleagues recruited treatment-resistant patients with the most common form of lupus, called systemic lupus erythematosus (SLE). All trial participants showed damage to multiple organs, including the kidneys, heart, lungs and joints.
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After treatment, the five participants’ B-cell counts plummeted, as did their autoantibody levels. Their lupus symptoms subsided and all stopped taking their previous medications, and so far, no patient has relapsed. The first patient treated, whose case was initially described in New England Journal of Medicine (opens in a new tab) — has now been in drug-free remission for 17 months.
“He lives a completely normal life,” Schett said.
Notably, five months after treatment, the patient’s B-cell count began to rise, but her symptoms did not return. Because the horde of dysfunctional B cells had been wiped out of the body, the bone marrow began producing new “baby” B cells that don’t pump out the same autoantibodies that their predecessors did, he said. Schett.
The other four patients also started producing new B cells within months of treatment, without relapse. It appears that restarting the B-cell system in this way could prevent the disease from returning, but they will need to keep monitoring the patients to be sure, Schett said.
“The median follow-up of 8 months is too early to determine whether it’s a complete remission,” said Dr. Jean Yean-jin Lin, instructor of medicine (rheumatology) at Northwestern University Feinberg School of Medicine, who did not participate in the trial. “It is possible that these naïve B cells over time re-encounter self-antigens and become autoreactive,” Lin told Live Science in an email.
None of the patients developed cytokine release syndrome or other serious side effects, but that may not be true for all lupus patients, he noted. “The tolerability looked good, but when more patients are treated, more side effects will probably surface,” Dr. Ronald van Vollenhoven, a professor of rheumatology at the University of Amsterdam Medical Centers who was not involved, told Live Science in the essay an email
Schett and his team are organizing a larger trial of CAR T-cell therapy for lupus, as well as the autoimmune diseases systemic sclerosis and myositis. In the future, the therapy could also be tested as a treatment for rheumatoid arthritis and multiple sclerosis, among other autoimmune disorders, Schett said.
If ultimately approved, CAR T for lupus “would be an option for patients who have very severe SLE and have not failed available treatments,” van Vollenhoven said. “Also in the long term, the question is whether this new therapy could achieve lasting remission or even a ‘cure’.”
“The potential of CAR T to reshape the immune system and lead to durable remission without treatment is exciting,” said Lin.
Originally published in Live Science.