CAR T-Cell Therapy Side Effects in Autoimmune Disease

Chimeric antigen receptor (CAR) T-cell therapy, which was pioneered in the cancer field, has been applied to treat severe autoimmune diseases. In CAR T-cell therapy, engineered T-cells target and eliminate B cells, including those that can cause autoimmune reactions. Due to its relatively short history in treating autoimmune diseases, the side effects of CAR T-cell therapy in this context are still being understood.

In a new study published in The Lancet Rheumatology, researchers examined local organ-specific reactions after CAR T-cell therapy and identified a previously unreported side effect, which they termed local immune effector cell-associated toxicity syndrome (LICATS). The study involved patients with SLE, idiopathic inflammatory myopathy, and systemic sclerosis. Of the 39 patients, 77% experienced a total of 54 LICATS events. These mild, self-limited inflammatory reactions resembled symptoms of the patients’ original disease but resolved on their own. Biopsies confirmed there were no signs of autoimmune reactivation. The most affected organs included the skin (rashes) and kidneys (proteinuria), and symptoms appeared a median of 10 days after CAR T-cell infusion and lasted around 11 days.

LICATS is different from other serious side effects like cytokine release syndrome, and it’s also not a sign that the autoimmune disease is coming back. Instead, researchers believe these mild symptoms may occur because the body is clearing out leftover dead B cells and debris from the tissues affected by the disease. Because LICATS goes away on its own and isn’t caused by active autoimmunity, it usually doesn’t need treatment with immunosuppressing drugs. Understanding LICATS as its own, mostly harmless reaction helps doctors know what to expect and how to care for patients during future CAR T-cell trials for autoimmune disease.

CAR T-cell therapy has shown promise in treating autoimmune diseases, though its use is still considered experimental as long-term studies are necessary to evaluate its safety, durability, and impact on disease relapse. This new observational study aims to clarify the short-term inflammatory effects patients may experience and how these effects differ from more severe autoimmune complications.

Citation

Hagen et al. Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease: an observational study. The Lancel Rheumatology 7(6): E424-E433. DOI: https://doi.org/10.1016/S2665-9913(25)00091-8