Cell and gene therapy are being explored as potential treatments for a number of autoimmune diseases. — Photos: AP
Scientists are trying a revolutionary new approach to treat rheumatoid arthritis, multiple sclerosis, lupus and other devastating autoimmune diseases – by reprogramming patients’ out-of-whack immune systems.
When your body’s immune cells attack you instead of protecting you, today’s treatments tamp down the friendly fire, but they don’t fix what’s causing it.
Patients face a lifetime of pricey pills, shots or infusions with some serious side effects – and all too often, the drugs aren’t enough to keep their disease in check.
“We’re entering a new era,” said Johns Hopkins University rheumatologist Asst Prof Dr Maximilian Konig, who’s studying some of the possible new treatments in the United States.
They offer “the chance to control disease in a way we’ve never seen before”.
How?
Researchers are altering dysfunctional immune systems, not just suppressing them, in a variety of ways that aim to be more potent and more precise than current therapies.
They’re highly experimental, and because of potential side effects, largely restricted so far to patients who’ve exhausted today’s treatments.
But people entering early-stage studies are grasping for hope.
Starting with lupus
“What the heck is wrong with my body?” Mileydy Gonzalez, 35, of New York, US, remembers crying, frustrated that nothing was helping her daily lupus pain.
Diagnosed at 24, her disease was worsening, attacking her lungs and kidneys.
Gonzalez was having trouble breathing, needed help to stand and walk, and couldn’t pick up her three-year-old son, when last July (2024), her doctor at NYU Langone Health suggested the hospital’s study using a treatment adapted from cancer.
She had never heard of CAR-T (chimeric antigen receptor T cell) therapy, but decided: “I’m going to trust you.”
Over several months, she slowly regained energy and strength.
“I can actually run, I can chase my kid,” said Gonzalez, who is now pain- and pill-free.
“I had forgotten what it was to be me.”
CAR-T was developed to wipe out hard-to-treat blood cancers.
But the cells that go bad in leukaemias and lymphomas – immune cells called B cells – go awry in a different way in many autoimmune diseases.
Some American studies in mice suggested CAR-T therapy might help those diseases.
Then in Germany, University of Erlangen-Nuremberg immunologist Prof Dr Georg Schett tried it with a severely ill young woman who had failed other lupus treatments.
After one infusion, she’s been in remission – with no other medicine – since March 2021.
Using T cells
Last month (October 2025), Prof Schett told a meeting of the American College of Rheumatology how his team gradually treated a few dozen more patients, with additional diseases such as myositis and scleroderma, and few relapses so far.
Those early results were “shocking”, Dr Konig recalled.
They led to an explosion of clinical trials testing CAR-T therapy in the US and abroad for a growing list of autoimmune diseases.
How it works: Immune soldiers called T cells are filtered out of a patient’s blood and sent to a lab, where they’re programmed to destroy their B cell relatives.
After some chemotherapy to wipe out additional immune cells, millions of copies of those “living drugs” are infused back into the patient.
While autoimmune drugs can target certain B cells, experts say they can’t get rid of those hidden deep in the body.
CAR-T therapy targets both the problem B cells and healthy ones that might eventually run amok.
Prof Schett theorises that the deep depletion reboots the immune system so that when new B cells eventually form, they’re healthy.
CAR-T is grueling, time-consuming and costly, in part because it is customised.
A CAR-T cancer treatment can cost US$500,000 (RM2.06mil).
Now, some companies are testing off-the-shelf versions, made in advance using cells from healthy donors.
In this image of a pancreatic lymph node from a mouse in Prof Green’s lab, red marks the bad T cells that destroy insulin production, whileyellow indicates the peacemaker regulatory T cells that counterautoimmune responses.
Other methods
Another approach uses “peacekeeper” cells at the centre of this year’s (2025) Nobel Prize in Physiology or Medicine.
Regulatory T cells are a rare subset of T cells that tamp down inflammation and help hold back other cells that mistakenly attack healthy tissue.
Some biotech companies are engineering cells from patients with rheumatoid arthritis and other diseases, not to attack like CAR-T does, but instead, to calm autoimmune reactions.
Scientists are also repurposing another cancer treatment, drugs called T cell engagers, that don’t require custom engineering.
These lab-made antibodies act like a matchmaker.
They redirect the body’s existing T cells to target antibody-producing B cells, said physician-scientist Prof Dr Ricardo Grieshaber-Bouyer, who works with Prof Schett and also studies possible alternatives to CAR-T.
Last month (October 2025), Prof Grieshaber-Bouyer reported giving a course of one such drug, teclistamab, to 10 patients with a variety of diseases including Sjögren’s, myositis and systemic sclerosis.
All but one improved significantly and six went into drug-free remission.
Rather than wiping out swaths of the immune system, Dr Konig aims to get more precise, targeting “only that very small population of rogue cells that really causes the damage”.
B cells have identifiers, like biological barcodes, showing they can produce faulty anti- bodies, he said.
Researchers in his lab are trying to engineer T cell engagers that would only mark “bad” B cells for destruction, leaving healthy ones in place to fight infection.
Targeting type 1 diabetes
Nearby in another Hopkins lab, biomedical engineer Prof Dr Jordan Green is crafting a way for the immune system to reprogramme itself with the help of instructions delivered by messenger ribonucleic acid (mRNA), the genetic code used in certain Covid-19 vaccines.
In his lab, a computer screen shines with brightly-coloured dots that resemble a galaxy.
It’s a biological map that shows insulin-producing cells in the pancreas of a mouse.
Red marks rogue T cells that destroy insulin production.
Yellow indicates those peacemaker regulatory T cells – and they’re outnumbered.
Prof Green’s team aims to use mRNA to instruct certain immune “generals” to curb the bad T cells and send in more peacemakers.
They package the mRNA in biodegradable nanoparticles that can be injected like a drug.
When the right immune cells get the messages, the hope is they’d “divide, divide, divide and make a whole army of healthy cells that then help treat the disease”, Prof Green said.
The researchers will know it’s working if that galaxy-like map shows less red and more yellow.
Studies in people are still a few years away.
A drug for type 1 diabetes “is forging the path”, said University of Colorado Anschutz rheumato- logist Prof Dr Kevin Deane.
Type 1 diabetes develops gradually, and blood tests can spot people who are brewing it.
A course of the drug teplizumab is approved to delay the first symptoms, modulating rogue T cells and prolonging insulin production.
Exploring rheumatoid arthritis
Prof Deane studies rheumatoid arthritis and hopes to find a similar way to block the joint-destroying disease.
About 30% of people with a certain self-reactive antibody in their blood will eventually develop the condition.
A new study tracked some of those people for seven years, mapping immune changes leading to the disease long before joints become swollen or painful.
Those changes are potential drug targets, Prof Deane said.
While researchers hunt possible compounds to test, he’s leading another study called StopRA: National to find and learn from more at-risk people.
Hoping for a cure
On all these fronts, there’s a tremendous amount of research left to do – and no guarantees.
There are questions about CAR-T’s safety and how long its effects last, but it is furthest along in testing.
ALSO READ: Creating a ‘suit of armour’ for CAR T cancer-fighting cells
Allie Rubin, 60, of Boca Raton, Florida, US, spent three decades battling lupus, including scary hospitalisations when it attacked her spinal cord.
But she qualified for CAR-T when she also developed lymphoma – and while a serious side effect delayed her recovery, next month will mark two years without a sign of either cancer or lupus.
“I just remember I woke up one day and thought, ‘Oh my god, I don’t feel sick anymore’,” she said.
That kind of result has researchers optimistic.
“We’ve never been closer to getting to – and we don’t like to say it – a potential cure,” said Dr Konig.
“I think the next 10 years will dramatically change our field forever.” – AP
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