Five patients with hard-to-treat lupus went into remission after scientists changed their immune cells using a technique commonly used to treat cancer. After the single therapy, all five patients with autoimmune disease stopped their standard treatments and did not 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 studies, the therapy could someday 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 Erlangen-Nuremberg in Germany. Sheth is senior author of a new report describing the small process, which was published Thursday (Sept. 15) in the journal Natural medicine (opens in new tab).
“It’s one injection of CAR T cells, and patients stop all treatments,” Sheth told Live Science. “We were really surprised [at] how good is this effect.”
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Rebooting the immune system
Lupus is a chronic disease in which immune system it inadvertently attacks the body’s own cells, leading to inflammation, tissue damage, pain and fatigue. Symptoms, which range from mild to life-threatening, can occur in “flares” and patients often take multiple medications to reduce their frequency and severity.
In lupus, dysfunctional B cells, a type of immune cell, pump out “autoantibodies” that enter the body’s cells and call on other cells to destroy them. Several drugs target these harmful B cells, but they don’t work in all lupus patients.
“There is a group that is really very severe and they go through several therapies and never go into remission,” Sheth said.
Schett’s group theorizes that such treatment-resistant lupus patients could potentially benefit from CAR T-cell therapy, which has previously been used to treat crab patients. During CAR T-cell therapy, doctors extract immune cells, called T cells, from the patient’s blood, genetically altering these T cells in the laboratory and then injecting them back into the patient’s body, according to the NIH National Cancer Institute (opens in new tab) (NCI). In all approved cancer therapies, these engineered T cells target B cells with specific molecules on their surfaces, destroying both the 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 suddenly unleash a flood of inflammatory molecules into the bloodstream. flow. So, despite the potential benefits, the treatment is not suitable for those with only mild disease.
For their experiment, Sheth and his 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, all five participants’ B-cell counts dropped sharply, as did their autoantibody levels. Their lupus symptoms subsided and they all stopped taking their previous medications, and so far no patient has relapsed. The first patient treated—whose case was originally described in New England Journal of Medicine (opens in new tab) — has now been in drug-free remission for 17 months.
“She lives a completely normal life,” Sheth said.
Notably, five months after treatment, the patient’s B-cell count began to rise, but her symptoms did not return. As the horde of dysfunctional B cells was culled from the body, the bone marrow began producing new “baby” B cells that didn’t pump out the same autoantibodies as their predecessors, Sheth said.
The other four patients also began producing new B cells within months of treatment, without relapse. It appears that restarting the B-cell system in this way may prevent the disease from returning — but they will need to continue monitoring the patients to be sure, Sheth said.
“A median follow-up of 8 months is too early to determine if this is a complete remission,” said Dr. Jean Yean-jin Lin, instructor of medicine (rheumatology) at Northwestern University Feinberg School of Medicine, who was not involved in the legal process. “It is possible that these naïve B cells may re-encounter self-antigens over time 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, she noted. “Tolerability seemed good, but as more patients are treated, more side effects will likely surface,” Dr. Ronald van Vollenhoven, a professor of rheumatology at the University of Amsterdam Medical Centers who was not involved in the trial, told Live Science in 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 diseases, Sheth said.
If ultimately approved, CAR T for lupus “will be an option for patients who have very severe SLE and who have failed with available treatments,” van Vollenhoven said. “In the longer term, the question is whether this new therapy can achieve long-lasting remission or even a ‘cure’.”
“The potential for CAR T to alter the immune system and lead to durable remission without treatment is exciting,” Lin said.
Originally published on Live Science.