EBMT 2026 | The rapidly evolving field of CAR-T: developing approaches for MF, autoimmune disease & solid tumors

CAR T-cells from their inception in the early 90s, they have gone a long way into the products that we have available now. We had the first generation CAR T-cells that didn’t work so well and then the fantastic success of the second generation CAR T-cells that we now use in clinic and there are quite a few licensed products for B-cell malignancies. But now we’re moving into a new era, the era of the third generation or armored CAR T-cells or some people call them TRUCKs. 

So the amazing thing about CAR T-cells are that it’s not a single therapeutic agent. They are cells that we can instruct them, we can engineer them to do something specifically. In most cases, this is to go after a tumor cell, but they can do other stuff. For example, they can secrete a therapeutic payload within the tumor microenvironment, actively changing the conditions and hopefully attracting other immune cells and being able to turbo boost the immune response against cancers. But more recently, we have seen that they can actually go after normal cells, like normal B lymphocytes, and by doing that, they are resetting the B lymphocyte compartment, and that can be curative for autoimmune diseases. We have some very promising trials in SLE or multiple sclerosis, and I’m sure that we’ll have some approved products for autoimmune disorders. At UCL, we have an active trial using obe-cel, which was initially developed for B-cell acute lymphoblastic leukemia, but now it’s being repurposed to target SLE and hopefully in the future membranous glomerulonephritis. 

However, there have been some other advancements in CAR T-cells and now moving into my work which will be to develop CAR T-cells for myelofibrosis. A third of cases of myelofibrosis are caused by the calreticulin mutation which is a very interesting cancer neoantigen. Because in order to drive the disease, in order to drive the malignant stem cell clone, it has to be expressed on the surface, activating aberrantly the thrombopoietin receptor. Now, most cancers will hide their mutations, most neoantigens will be hidden within the nuclear compartment or within the cell, so calreticulin is very unique because it shows itself to the immune system. And hence, it’s an excellent immunotherapeutic target and there are actually ongoing phase one trials using monoclonal antibodies and bispecific T-cell engagers. But at UCL, in collaboration with Oxford, we developed the first CAR T-cell therapy, which in a way is the most important immunotherapy to go after this target. Our data should be available hopefully very soon for everyone to read and study and we’re very hopeful that within the next 12 months we will be able to launch a phase one clinical trial aiming for the first time in myelofibrosis to cure the disease outside, obviously, the context of a stem cell transplant. So we’re very excited about that. 

I think the CAR-T field is expanding, is advancing into new territories. I think the last thing remaining is how we can tackle solid tumors. But again, there have been some trials that are very promising. The armored CAR T-cells we discussed earlier on may hold the key to actively changing the tumor microenvironment and overcoming the challenges that solid tumors pose, that these challenges are not always there for hematological cancers. So everyone interested in CAR T-cells, I think this is probably the most exciting time and we can see that within a generation, hopefully, we will have many, many curative treatments for most malignancies, but also for some autoimmune disorders or even anti-aging CAR T-cells. We had a talk by Dr Corina Amor earlier on during EBMT, where she described how CAR T-cells can clear senescent cells, revitalizing organs, and potentially reversing aging in mice. So it’s all very exciting. So I would encourage everyone to connect and to study and work on the CAR-T field.

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