Scientists are trying a revolutionary new approach to treating rheumatoid arthritis, multiple sclerosis, lupus and other diseases. devastating autoimmune diseases — by reprogramming the patients’ immune system that has failed.
When your body immune cells attack you Instead of protecting you, today's procedures extinguish friendly fire, but do not eliminate its cause. Patients face lifelong expensive pills, shots or infusions with serious side effects – and too often the drugs are not enough to keep the disease under control.
“We're entering a new era,” said Dr. Maximilian Koenig, a rheumatologist at Johns Hopkins University who is studying some of the possible new treatments. They offer “the chance to control disease in a way we've never seen before.”
How? Researchers are modifying the dysfunctional immune system, rather than simply suppressing it, in a variety of ways, aiming to be more effective and precise than current treatments.
They are highly experimental and, due to potential side effects, are still mainly reserved for patients who have exhausted the options of current treatments. But people who begin research in the early stages cling to hope.
“What the hell is wrong with my body?” Mailidi Gonzalez, 35, of New York City, remembers crying, frustrated that nothing was helping her daily pain from lupus.
When she was diagnosed at 24, her illness was worsening, affecting her lungs and kidneys. Gonzalez had trouble breathing, needed help to stand and walk, and was unable to hold her 3-year-old son when her doctor at NYU Langone Health suggested a hospital trial last July using a treatment adapted for cancer.
Gonzalez had never heard of CAR-T therapy, but decided, “I’m going to trust you.” Over the course of several months, she slowly regained her energy and strength.
“I can actually run around, chase my baby,” said Gonzalez, who is now pain- and pill-free. “I forgot what it means to be myself.”
CAR-T was developed to combat difficult-to-treat blood cancers. But the cells that go bad in leukemia and lymphoma—immune cells called B cells—fail differently in many autoimmune diseases.
Some American studies in mice have shown that CAR-T therapy may help treat these diseases. Then in Germany, Dr. Georg Schett from the University of Erlangen-Nuremberg tried this method on a seriously ill young woman for whom other treatments for lupus had failed. After one infusion, she has been in remission—without any other medications—since March 2021.
Schett told a meeting of the American College of Rheumatology last month how his team has gradually treated dozens more patients with additional diseases such as myositis and scleroderma, with few relapses so far.
Those early results were “shocking,” Hopkins’ Koenig recalls.
They have led to an explosion of clinical trials of CAR-T therapies in the United States and abroad for a growing list of autoimmune diseases.
How it works: Immune soldiers called T cells are filtered from a patient's blood and sent to a laboratory where they are programmed to destroy their B cell cousins. After some chemotherapy aimed at destroying additional immune cells, millions of copies of these “live drugs” are injected back into the patient.
Although autoimmune drugs can target certain B cells, experts say they cannot get rid of those hidden deep in the body. CAR-T therapy targets both problem B cells and healthy ones that may eventually run out of control. Schett theorizes that profound exhaustion resets the immune system so that when new B cells are eventually produced, they are healthy.
CAR-T is a grueling, time-consuming and expensive process, in part because it varies from person to person. CAR-T cancer treatments can cost $500,000. Some companies are now testing ready-made versions made in advance using cells from healthy donors.
Another approach uses “peacekeeper” cells on center of this year's Nobel Prize. Regulatory T cells are a rare group of T cells that suppress inflammation and help keep other cells at bay that mistakenly attack healthy tissue. Some biotech companies are engineering cells from patients with rheumatoid arthritis and other diseases not to attack, as CAR-T does, but to calm autoimmune reactions.
Scientists are also repurposing another cancer treatment, drugs called T-cell activators, which do not require special development. These laboratory antibodies act as a matchmaker. They redirect the body's existing T cells to antibody-producing B cells, says Dr. Ricardo Grieshaber-Buyer of Erlangen, who is working with Schett and also studying possible alternatives to CAR-T.
Last month, Grieshaber-Buyer reported administering a course of one such drug, teclistamab, to 10 patients with a variety of conditions, including Sjögren's disease, myositis and systemic sclerosis. All but one experienced significant improvement in their condition, and six experienced drug-free remission.
Instead of targeting specific areas of the immune system, Hopkins' Koenig aims to become more precise, targeting “only that very small population of rogue cells that actually do the damage.”
According to Koenig, B cells have identifiers similar to biological barcodes, indicating that they can produce defective antibodies. Researchers in his lab are trying to create T-cell activators that will tag only “bad” B cells for destruction, leaving healthy ones to fight infection.
Nearby, in another Hopkins lab, biomedical engineer Jordan Green is developing a way to reprogram the immune system using instructions carried by messenger RNA, or mRNA, the genetic code used in COVID-19 vaccines.
In Green's lab, the computer screen glows with bright dots that resemble a galaxy. This is a biological map showing the insulin-producing cells of a mouse pancreas. In red are rogue T cells that disrupt insulin production. The yellow color indicates these peacekeeping regulatory T cells and are less abundant.
Green's team intends to use this mRNA to instruct certain immune “generals” to rein in the bad T cells and send out more peacekeepers. They package the mRNA into biodegradable nanoparticles that can be administered as a drug. Once the right immune cells get the message, the hope is that they will “divide, divide, divide and create an army of healthy cells that then help treat the disease,” Green said.
Researchers will know it's working if the galaxy-like map has less red and more yellow. Human studies are still several years away.
A cure for type 1 diabetes is “paving the way,” said Dr. Kevin Dean of the University of Colorado Anschutz.
Type 1 diabetes develops gradually, and blood tests can identify people who develop it. A course of the drug teplizumab has been approved to delay the first symptoms, modulate rogue T cells and prolong insulin production.
Dean studies rheumatoid arthritis and hopes to find a similar way to block the joint-destroying disease.
About 30% of people with certain autoreactive antibodies in their blood eventually develop RA. The new study tracked some of these people for seven years, mapping the immune changes that lead to the disease long before the joints become swollen or painful.
These changes are potential drug targets, Dean said. While researchers are looking for possible compounds to test, he is leading another study called StopRA: National to find and learn from at-risk people.
There is a huge amount of research to be done in all these areas – and there are no guarantees. There are questions about the safety of CAR-T and how long its effects last, but it is the furthest along in trials.
Ellie Rubin, 60, of Boca Raton, Florida, spent three decades battling lupus, including terrifying hospitalizations when it attacked her spinal cord. But she became eligible for CAR-T when she also developed lymphoma — and although a serious side effect delayed her recovery, next month she will mark two years without signs of cancer or lupus.
“I just remember waking up one day and being like, 'Oh my God, I'm not going to be sick anymore,'” she said.
This result gives researchers optimism.
“We've never been closer to a potential cure—and we don't like to say it,” Hopkins' Koenig said. “I think the next 10 years will fundamentally change our industry forever.”
—
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Department of Science Education and the Robert Wood Johnson Foundation. AP is solely responsible for all content.
