German rheumatologists conducted an observational study and identified a previously unknown side effect of therapy for autoimmune diseases using lymphocytes with chimeric antigen receptors. It is likely related to the abrupt elimination of immune cells from affected tissues. In most cases, this complication is mild and resolves spontaneously over time. The study was published in The Lancet Rheumatology.
Chimeric antigen receptor T-cell (CAR-T) technology (detailed in the article "Chimera vs. Cancer") was developed and is used primarily for the treatment of malignant neoplasms. The greatest success has been achieved in the treatment of B-cell hematological malignancies with autologous anti-CD19 CAR-T cells. In pilot clinical trials, similar cells have been successfully used to treat various severe autoimmune diseases (the editors of Science, like Nature, named these experiments one of the key scientific achievements of 2024). The most common side effects specific to this treatment method include ICANS syndrome and other manifestations of neurotoxicity, cytokine release syndrome, and hemophagocytic lymphohistiocytosis.
Georg Schett of the Friedrich-Alexander University of Erlangen and Nuremberg and colleagues analyzed organ-specific responses to CD19-CAR T-cell therapy for autoimmune diseases in their clinical trials. The analysis included 39 patients (median age 36 years, 64 percent women) treated at two clinical centers from March 2021 to October 2024. Twenty of them had systemic lupus erythematosus, 13 had systemic sclerosis, and six had idiopathic inflammatory myopathy.
Following treatment, 54 local toxic reactions were reported in 30 patients (77 percent). The median time of onset was 10 days after CAR-T cell infusion, and the median duration was 11 days. All of these events occurred only during the B-cell aplasia phase and affected only organs affected by the autoimmune disease—most commonly, the skin (35 percent of events) and kidneys (22 percent). Most of these events were relatively mild, with only three cases being severe (prolonging hospitalization or requiring repeat hospitalization). All were uneventful.
The researchers dubbed the new side effect local immune effector cell-associated toxicity syndrome (LICATS). They believe that temporary dysfunction of the affected organs results from local inflammation due to the massive death of tissue-infiltrating B lymphocytes. LICATS should be differentiated from cytokine release syndrome during clinical trials, as it is localized and self-limited and does not require resumption of immunosuppressive therapy, the authors believe.
A previous analysis of long-term outcomes of experimental CAR-T cell therapy confirmed an extremely low risk of developing new tumors. Phase II clinical trials also demonstrated that this treatment method is quite effective and safe when administered in an outpatient setting. However, the leading cause of non-cancer death after CAR-T therapy was infections.
