CAR-T therapy

Engineered T cells that have been used to treat ulcerative colitis, rheumatoid arthritis and lupus show promising results.

NEWS Nature: November 26, 2026

Engineered immune cells are being used to successfully treat people with a range of debilitating autoimmune conditions, such as ulcerative colitis, rheumatoid arthritis and lupus. Researchers say positive results from around a dozen studies over the past three years suggest CAR-T-cell therapy could eventually be used treat any disease in which the immune system attacks the body.

CAR-T-cell therapy exploits the immune system’s T cells that fight off infection: these cells are collected from a person and tweaked to produce proteins called chimeric antigen receptors. They are then reintroduced into the body to target antigens expressed by B cells, another type of immune cell. In autoimmune disorders, these B cells make antibodies that attack the body’s own healthy tissues.

The use of the therapy for immune conditions has exploded since 2021, when a 20-year-old woman in Germany with severe lupus became the first person with an autoimmune disorder to be treated with CAR T cells. Clinician–researcher David Simon, who was involved in that treatment , says the CAR-T therapies have since entered phase I and II clinical trials for autoimmune conditions including systemic sclerosis, myositis and rheumatoid arthritis. Phase III trials are also under way for lupus and myasthenia gravis, a condition that causes weakness in the muscles that are used to breathe, swallow and see.

Simon, who focuses on rheumatoid arthritis at the Charité University Hospital in Berlin, says people in CAR-T-cell therapy trials for rheumatoid arthritis and lupus seem to be ‘cured’. “They lose their autoantibodies which trigger the disease, and they don’t have any symptoms anymore,” he adds. “This is something totally new which we didn’t observe before.”
 
NEJM: Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell–engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants.
 
If daratumumab turns out to work, perhaps this anti CD38 CAR-T will be the future of ME/CFS treatment

 
However, I think MECFS isn't one, but rather a brain disease. How would CAR T cell therapy be useful? Sorry, I don't really understand it.

CAR-T cells can be used to target all sorts of things. In this case, antibody producing B cells are being targeted in lupus (by my old PhD student Maria at UCH) so the treatment is really just a technical variant of rituximab that might have a longer lasting effect. So far we don't know but are hoping.

We don't now to what extent immune and brain signals are the continuing problem in ME/CFS. Antibodies may be continuing to trigger signals that disturb the brain. We do not have good evidence of autoantibodies but, as we put in our Qeios paper, there are ways antibodies might mediate problems without being autoantibodies per se.

I am farily sceptical about targeting antibodies but I would not rule it out. CAR-T does not seem to me a sensible way forward to test a role for antibody because it is toxic, expensive and may not test the theory any better than rituximab. Daratumumab is a more interesting option because it might do what riuximab didn't do that might be crucial - get rid of long lived plasma cells.
 
I dont know if its the right place to ask, but I was wondering if IVIG response is a good test for autoimmunity?

IVIG is a pretty rubbish treatment for anything except perhaps acute immune thrombocytopenia. There is pretty little evidence that it has a major useful impact on any other autoimmune disease. Unsurprisingly, since there isn't any very good reason why it should as far as I know.
 
Woman who had been bedbound with severe lupus affecting multiple organs was interviewed. Was presented as now well.
Loosely related, but I would be very interested in how the process of recovering from this goes, how much physical rehabilitation is required, and how long it takes. My guess is: none, and not long. It's a gradual process, but it obviously doesn't require any such assistance, or being taught how to do it.
 
Loosely related, but I would be very interested in how the process of recovering from this goes, how much physical rehabilitation is required, and how long it takes. My guess is: none, and not long. It's a gradual process, but it obviously doesn't require any such assistance, or being taught how to do it.

No physical rehabilitation is even considered. Patients do more as they get well. I would expect the effect of CD19 CAR-T to have the same time frame as rituximab. The benefit in RA occurs gradually over a period of 3 months, and sometimes a bit longer. In lupus autoantibody levels can fall very quickly - especially anti-dsDNA. The rate of clinical improvement depends on the feature - whether thrombocytopenia, which often improves very quickly (within a couple of weeks) or proteinuria, which tends to improve gradually as glomerular basement membranes recover over a few months.
 
No physical rehabilitation is even considered. Patients do more as they get well.
That's pretty much what I expect. It has huge implications on the same idea applied to us. If people bedbound by a "real" disease don't need rehabilitation, to the point where it's usually not even considered, how does it make sense for us? And for people who are mildly functional? This should matter! In a sane world it would.

If at least there was some minimal concern with making coherent arguments, this would all be so much less insulting. But psychosomatic stuff has all the "very special boy" exemptions that allow complete nonsense to dominate.
 
IVIG is a pretty rubbish treatment for anything except perhaps acute immune thrombocytopenia. There is pretty little evidence that it has a major useful impact on any other autoimmune disease. Unsurprisingly, since there isn't any very good reason why it should as far as I know.
Would the verdict for Immunoadsorption as a test for autoimmunity be similar?

Would a non-response to IA mean that we could rule out that targeting LLPC with daratumumab will have any benefit over the failed rituximab?
 
Would the verdict for Immunoadsorption as a test for autoimmunity be similar?

If immunoadsorption clears a significant proportion of autoantibody it may be effective. Immunoadsorption covers a range of techniques so I don't think there is one answer. In the past plasmapheresis has been used to remove autoantibodies and it can be useful for myasthenia gravis I am told. At least immunoadsorption has a straightforward rationale - just clearing ut autoantibody.

I don't think a non-response to immunoadsorption is a reliable guide to whether targeting long lived plasma cells will be useful. There are lots of complications around how long the effect lasts, how long it takes for the disease to 'unwind' once antibodies are cleared etc. etc.
 
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