I would like to wish all my readers a happy, joyful and above all healthy new year 2024. At the beginning of a year, one is sometimes asked where one sees interesting potentials in terms of therapeutic developments. Naturally, several exciting aspects come to mind. But I would argue that one of the most exciting developments in the therapy of autoimmune diseases are the advances in so-called CAR-T cells. Therefore, here is an outlook on CAR-T cell therapy for Multiple Sclerosis (MS).
The acronym CAR stands for “chimeric antigen receptor” – so it is a therapy with T-lymphocytes, which have been genetically modified in the lab to carry a chimeric antigen receptor (CAR). And it is designed to recognize a specific antigen on the surface of a target cell.
CAR-T Cell Therapy: Origin
CAR-T cells were originally developed and used for the treatment of cancer. The modified T-cells are given to the cancer patient through an infusion, circulate in the body and look for the specific cancer cells that carry the target antigen. As soon as the CAR-T cells recognize the cancer cells and engage in receptor binding, they are able to destroy the cancer cells. This type of therapy has already proven to be very effective for certain forms of blood cancer.
CAR-T Cell Therapy: Autoimmune Diseases
For some time now, researchers have begun to use CAR-T cells in the treatment of autoimmune diseases. Pioneers in Germany was the Rheumatology department of the University Hospital Erlangen, which in 2022 published the successful treatment of a young patient with therapy-resistant lupus erythematosus (SLE) in the renowned medical journal Nature Medicine (Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus – PubMed (nih.gov)).
SLE is a serious autoimmune disease that can potentially affect any organ system and is mediated by autoantibodies against various cellular components. Since autoantibodies are produced by so-called B-lymphocytes, CAR-T cells against the surface molecule CD19 were used to treat the young SLE patient. CD19 is a surface marker of B-lymphocytes (B-cells), which can therefore be recognized and destroyed by the anti-CD19 CAR-T cells. With this new therapeutic concept, a remission of the autoimmune disease was achieved in the SLE patient, after this had previously not been achieved with many other, partially highly effective therapies.
In light of this therapeutic success, anti-CD19 CAR-T cells were subsequently used not only in rheumatology, but first experiences were also gained with neurological diseases, especially with Myasthenia gravis, an acquired muscle weakness that is also mediated by autoantibodies against the acetylcholine receptor on muscle cells. Here too, the first case reports on the treatment of therapy-resistant Myasthenia patients are very promising (Anti-CD19 CAR T cells for refractory myasthenia gravis – PubMed (nih.gov)).
CAR-T Cell Therapy: Multiple Sclerosis
It has been shown in recent years that B-cells also play an important role in the pathogenesis of Multiple Sclerosis. This is supported not least by the fact that B-cell-depleting therapies (Rituximab, Ocrrelizumab, Ofatumumab, Ublituximab) are currently considered highly effective therapeutic concepts for the treatment of relapsing MS. It has also become clear in recent years that B-cells are important for the chronic progression of the disease. Especially in chronic courses, B-cell aggregations were found in the brain that correlate with the extent of disability progression. The problem is that these B-cell aggregates cannot be reached with conventional systemic therapies. Therefore, a lot of energy is currently being focused on the development of CNS-accessible drugs that are directed against B-cells.
In this context, CAR-T cells directed against B-cells are also of great interest for the therapy of MS. A CAR-T cell therapy would at least theoretically be able to detect and destroy pathological B-cells in the CNS as part of immune surveillance. Therefore, it will be very exciting to see what happens here in the near future and whether such concepts may achieve successes in preventing chronic progression.
However, it must also be mentioned that a CAR-T cell therapy – especially in the treatment of cancer – can be associated with risks and serious side effects. These include the cytokine release syndrome (CRS): when the CAR-T cells attack other cells, they release cytokines that can trigger a strong immune response. In addition, the therapy can be neurotoxic, i.e., patients can develop central nervous system irritations and failures. It must also be said that such a therapy can initially only be carried out in highly specialized centers, which have a well-established cooperation between neurology and hematology, and is of course only meaningful for selected patients within the framework of study programs. But I still find this development extremely interesting with a view to the future.
See also the MS-Docblog text “New Cell Therapeutic Approaches“.
