At present, a small revolution is taking place in cancer therapy with the introduction of so-called CAR-T cells. These dynamic developments are now also increasingly affecting other areas of medicine, including multiple sclerosis. Therefore, I would like to write a few explanatory lines on the topic of cell therapy – also to facilitate my readers’ classification of news on this topic, which is increasingly circulating on the Internet.In therapy with CAR-T cells, T cells are removed from an individual. Outside the body (ex vivo), these cells are then genetically altered so that they express a so-called chimeric antigen receptor (CAR) on their surface – hence the name CAR-T cells. This genetically engineered antigen receptor is capable (as exclusively as possible) of recognizing a (tumor) antigen. The thus modified T cells are increased and implanted in the patient. Before such implantation, cancer patients are conditioned, i.e., their immune system is so downregulated by additional chemotherapy that favorable conditions for their proliferation exist in the patient’s organism for the introduced CAR-T cells.
Focus on Tumor Antigens
If the CAR-T cells now recognize a tumor cell, they become cytotoxic T cells that destroy the tumor cells after binding. In addition, CAR-T cells begin to proliferate after such activation, which can lead to an increase in effectiveness over time. Last but not least, the CAR-T cells remain longer in the patient and can become active again if the tumor reoccurs. Thus, CAR-T cells are a unique “drug” that has already led to astonishing successes in some tumors that were considered therapy-refractory. Currently, indications still predominate in the field of hematology – here, great therapeutic successes have been achieved with CD19-specific CAR-T cells in so-called B-cell leukemias. But the pharmaceutical industry is already focusing on other tumor antigens.
Of interest, for example, are cancer diseases associated with the Epstein-Barr virus (EBV), as here T-cell therapies directed against EBV can be used. Tabelecleucel (tab-cel®) is an allogeneic T-cell immunotherapy developed for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative syndrome (EBV+ PTLD) and is currently being tested in a phase III study.
Removing EBV-B Cells in Multiple Sclerosis?
And now it gets exciting with regard to MS: At the beginning of the year, a large epidemiological study again impressively demonstrated the connection between MS and EBV. Therefore, the idea of generating therapeutic benefit in MS by removing EBV-infected B cells through cell therapy is understandable.
This approach is pursued by the drug ATA188, which was developed by the same company as Tabelecleucel (tab-cel®). ATA188 is an allogeneic EBV-specific T-cell therapy that is selectively directed against EBV antigen-expressing cells that may play a role in the pathophysiology of MS. The effect of ATA188 is currently being tested in a multicenter Phase I/II study in patients with progressive MS (PPMS/SPMS) (EMBOLD, NCT03283826). Preliminary results of Phase I of the study were already communicated at the last ECTRIMS Congress and showed acceptable tolerability of the concept. The results of the Phase II EMBOLD study are expected in 2026.
I don’t want to pour cold water on the wine – but still two important remarks at the end. Please remember that the concept is only in the early phases of clinical testing. It is still completely unclear whether it has a significant effect and will ever receive approval. In addition, cell-based therapies are not entirely safe – especially the increased release of cytokines (“cytokine release syndrome”, CRS) is an important side effect. The CRS is accompanied by high fever, fatigue, nausea and cardiovascular disorders, and occasional fatal cases have been reported. Neurotoxicity has also been reported with the use of CAR-T cell therapies. This suggests that special attention must be paid to the safety aspect of cell therapies in MS, because chronic MS is not a life-threatening tumor disease in which even the most serious side effects are accepted.
