Five patients with hard-to-treat lupus entered remission after scientists tweaked their immune cells using a technique normally used to treat cancer. After the one-time therapy, all five patients with the autoimmune disease stopped their standard treatments and haven’t 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, clindamycin hcl wiki 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 Friedrich Alexander University Erlangen-Nuremberg in Germany. Schett is the senior author of a new report describing the small trial, which was published Thursday (Sept. 15) in the journal Nature Medicine (opens in new tab).
“It’s a single shot of CAR T cells and patients stop all treatments,” Schett told Live Science. “We were really surprised [at] how good this effect is.”
Rebooting the immune system
Lupus is a chronic disease in which the immune system inadvertently attacks the body’s own cells, resulting in inflammation, tissue damage, pain and fatigue. The symptoms, which range from mild to life threatening, can show up 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 out “autoantibodies” that glom onto the body’s cells and summon other cells to destroy them. Several medications target these harmful B cells, but they don’t work for all lupus patients.
“There is a group which is really very severe and they cycle through several therapies and never come into remission,” Schett said.
Schett’s group theorized that such 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 tweak those T cells in the lab and then inject them back into the patient’s body, according to the NIH’s National Cancer Institute (opens in new tab) (NCI). In all the approved cancer therapies, these engineered T cells target B cells with specific molecules on their surfaces, wiping out 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 a risk of triggering “cytokine release syndrome,” in which T cells suddenly unleash a flood of inflammatory molecules into the bloodstream. So, despite its potential benefits, the treatment isn’t appropriate for those who have only mild disease.
For their trial, Schett and his colleagues recruited treatment-resistant patients with the most common form of lupus, called systemic lupus erythematosus (SLE). All the trial participants showed damage in multiple organs, including the kidneys, heart, lungs and joints.
Following treatment, all five participants’ B cell counts plummeted, as did their autoantibody levels. Their lupus symptoms abated and they all stopped taking their prior medications, and so far, no patients have relapsed. The very first patient treated — whose case was initially described in the the 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,” Schett said.
Notably, five months post-treatment, the patient’s B cell count began to rise but her symptoms didn’t return. Since the horde of dysfunctional B cells had been annihilated from the body, the bone marrow began making new “baby” B cells that don’t pump out the same autoantibodies as their predecessors did, Schett said.
The other four patients’ also started making new B cells within months of treatment, without relapsing. It seems as though rebooting the B cell system in this way may prevent the disease from coming back — but they’ll need to keep monitoring the patients to be sure, Schett said.
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“The mean follow up of 8 months is too early to determine whether this is complete remission,” said Dr. Jean Yean-jin Lin, an instructor of medicine (rheumatology) at the Northwestern University Feinberg School of Medicine, who was not involved in the trial. “It’s possible that these naive B cells over time might 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 this may not hold true for all lupus patients, she noted. “The tolerability seemed ok but when more patients are treated more side-effects will likely come to the surface,” Dr. Ronald van Vollenhoven, a professor of rheumatology at Amsterdam University 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 disorders, Schett said.
If eventually approved, CAR T for lupus “would be an option for patients who have very severe SLE and who have failed available treatments,” van Vollenhoven said. “More long-term, the question is if this novel therapy could achieve long-lasting remission or even ‘cure.'”
“The potential for CAR T to reshape the immune system and lead to durable treatment free remission is exciting,” Lin said.
Originally published on Live Science.
Nicoletta Lanese is a staff writer for Live Science covering health and medicine, along with an assortment of biology, animal, environment and climate stories. She holds degrees in neuroscience and dance from the University of Florida and a graduate certificate in science communication from the University of California, Santa Cruz. Her work has appeared in The Scientist Magazine, Science News, The San Jose Mercury News and Mongabay, among other outlets.”};
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Nicoletta Lanese
Staff Writer
Nicoletta Lanese is a staff writer for Live Science covering health and medicine, along with an assortment of biology, animal, environment and climate stories. She holds degrees in neuroscience and dance from the University of Florida and a graduate certificate in science communication from the University of California, Santa Cruz. Her work has appeared in The Scientist Magazine, Science News, The San Jose Mercury News and Mongabay, among other outlets.
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