Nature: ‘It’s all gone’: CAR-T therapy forces autoimmune diseases into remission

I only ever met one person who had rheumatoid arthritis, an English woman who had moved to France with her family because she found better healthcare here. She said that when she has a rituximab injection, she feels so much better that she could go and run a marathon.

 

It is IgG and it is a substantial subset with antibodies against specific paranodal proteins.

In any case, the efficacy is when there is ongoing damage, rather than past damage.

 

Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome

https://www.pnas.org/doi/full/10.1073/pnas.2403227121

There's a pre/post video of the person's gait in the link provided.

SPS is the autoimmune condition that forced Celine Dion off stage by the way.

 

Seems like every nut is being cracked except for ME/CFS.

 

I didn't find an appropriate thread and am not sure whether it warrants its own thread, it possibly does, but in a newspaper article Scheibenbogen has declared that she will be trialling Inebilizumab, which depletes depletes CD19+ B cells, in Long-Covid respectively ME/CFS patients.

The article is paywalled, but some patients have reported the above:
https://www.welt.de/gesundheit/plus...-sind.html?cid=socialmedia.twitter.shared.web

 

If virus persistence is contributing to Long Covid B cell depletion would seem risky.

There were almost certainly excess deaths in patients on rituximab during the Covid epidemic and of course new variants are still making people ill and causing a few deaths.

 

Would it make sense for some of the B-cell experts to get involved? If only to design the trial in such a way that one can get more meaningful data on a possible role of plasmablasts and plasma cells?

 

Which B cell experts? Maybe Andreas Radbruch I guess.
Without an antibody to measure the only real issue is with re-treatment time. I suspect an initial trial will have to stick with a six month endpoint from a single infusion.

 

https://twitter.com/user/status/1812583399435239645


A new frontier: we have treated the first Multiple Sclerosis patient in the US with CAR-T immunotherapy (CD-19) in our Phase 1 Clinical Trial

 

Is this potentially huge for MS?

Protocol: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell ( CAR-T) Therapy in Subjects With Non-relapsing and Progressive Forms of Multiple Sclerosis

Paywalled article in Nature: CAR-T therapy for multiple sclerosis enters US trials for first time

 

not really. Nothing for Sjogrens, nothing for POTS/SFN which should have a separate trial like with Vyvgart, hope someone from BCMA/BAFF only trials recognizes this. there is an upcoming RA trial:
Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis

What else is new:

Schett's Myositis patient who relapsed 2 times with CD19 (actually, 2nd time didn't even improve), got BCMA CAR-T about 3 weeks ago, doesn't think she had toxicities and for now is having 'less muscle pains'.

I'd like to see data from IASO Bio as they have all 12 patients 2.5+ years follow-up, so if they don't relapse perhaps BCMA only is enough! But it seems they didn't share that data yet.

And there are some exciting case reports on allogeneic, with myositis, SLE and scleroderma. This might be big as it is much cheaper

I shared more on my FB group

Seems for now most relapses are within 6 months, which confirms previous advice to wait 6months data to see if some brand is good aka strong enough before taking anything experimental. To avoid developing anti-CAR antibodies because for now whoever had it repeated it failed 2nd time too (?) - (one SLE with cCAR-T and one myositis case from Schett).

 

I mentioned allogeneic CAR-T case reports (BRLmed a company who have also BCMA in the pipeline) in scleroderma and myositis.

The part I especially like:

https://www.shine.cn/news/metro/2407169316/

 

CAR-Ts sweep into autoimmunity



https://www.nature.com/articles/s41587-024-02321-0

 

What's new?

One SLE patient who got Cabaletta CD19 for lupus nephritis had a severe, grade 4 neurotoxicity (ICANS). It says she recovered after treatment and the study continues. Still scary, huh?!

other than this: for those who have small fiber neuropathy (SFN), and even better if you have also : POTS, suspected Sjogren's or any of the antibodies, I spoke with a researcher from Tongji University in China who published anti-BCMA reports for NMOSD /Sjogrens /RA /myositis /Myasthenia Gravis. The studies are very detailed, brand is IASO Bio, approved product in China for cancer, and they're now doing trials for MS, SLE and MG in USA. So the safety sounds promising. They also sold their CD19 to Cabaletta.

So this researcher/neuro is interested in treating SFN/POTS too as a part of IIT, so if anyone is actually interested, especially if you failed treatments like IVIG or Rituximab, contact me.
It might have to be paid so you'd have to be able to afford it. Hope we could avoid that part with setting up some IIT basket study

 

I would be interested in participating in this.

I was initially diagnosed with atypical MS as my symptoms were profound fatigue, dysautonomia and PEM. I technically met MS criteria because of white matter lesions on my brain MRI and 3 CSF specific oligoclonal bands on my LP. However, my symptoms are mostly related to chronic sore throat, fatigue with PEM, sleep disturbances and dysautonomia.

I have since had a skin biopsy which showed SFN and am scheduled for a lip biopsy in December to look for Sjogrens. I also had a muscle biopsy last year which showed mitochondrial abnormalities and underwent genetic testing with no inherited abnormalities. I have been on B cell depleting therapy for 3.5 years with worsening of symptoms without changes to my brain MRI. This is why my neurologist continues to look for alternative diagnosis.

I think I have some sort of autoimmune component but clearly anti CD20 therapy is not giving me any improvement. I also think my case is definitely CFS - I just have had a much more significant work up than the average patient. It helps that I was in healthcare and knew these physicians before I was sick. They are able to see the profound differences in me over these last few years.

Anyways - let me know about this CAR-T opportunity if you can.

 

Definitely sounds like Sjogrens!
I agree that you might be typical MECFS just more work up than the average patient.
Most have ANA measured only once and dismissed for years


You can also apply for Zheijang University trial (YaKe brand), if your Sjogrens is confirmed, but not sure if CNS involvement is exclusion criteria (i think so).
For IASO Bio anti-BCMA message me!

 

Switching off Autoimmunity

https://www.science.org/doi/10.1126/science.ade6949

 

More than 50 years ago, the immunologist Avrion Mitchison defined T cell help as a function that “lies at the heart of inflammation and other aspects of immunological and infectious disease”

Yes, well, dear old Av did as much as anyone to slow down the pace of autoimmune research. Fortunately, some of us ignored him. I remember one day he asked to come to my office to explain some things to me. That included his view that there is no such thing as scientific debate (i.e. immunology is just what Av Mitchison says it is). He also tried to persuade me that my work on B cells was totally misguided. I also remember him telling me I was dim in a paper to talk of myoid cells in the thymus when I meant myeloid cells. Strange from T cell biologists since myoid cells are unique to, and essential to, thymic (i.e. T) function.

OK, CD40 and CD40L are necessary components of the autoimmune process, but so is ATP. No doubt blocking immune responses indiscriminately will damp things down, but otherwise this seems to be about as Rip van Winkle (preferably pronounced Rip fon Vinkl) as you can get. At least CAR T CD19 is finally taking us a bit forward.

 

@Jonathan Edwards, will you go? https://hartleytaylor-registration.co.uk/docs/CARKprog.pdf