CAR T-cell therapy "Living drugs" in systemic lupus erythematosus

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative therapeutic option for patients with severe, refractory autoimmune conditions. Since 2022, several authors have published their experience using CAR T-cell therapy for patients with systemic lupus erythematosus (SLE).

This narrative review summarizes the biological rationale, diverse modalities, targets and platforms, the emerging clinical efficacy and safety data, as well as the barriers and innovations regarding the use of CAR T-cell therapy in SLE.

Among the 16 studies reviewed, 13 evaluated products targeting CD19 and the remaining three bispecific products targeting CD19 and B-cell maturation antigen (BCMA). Twelve studies assessed autologous therapies and four allogeneic products. Therapies evaluating CAR natural killer cells (CAR-NK), gamma delta T-cells (γδ T-cells), other transduction methods, and even in vivo CARs are currently being evaluated. Early data has demonstrated significant clinical efficacy, including rapid disease activity reductions, drug-free remission in over 80%, achievement of low-level disease activity in almost 90%, and remission in 70% of the patients where these outcomes were assessed. Cytokine release syndrome occurred in 56% of the patients evaluated, almost exclusively being grade 1 or 2 events, and neurotoxicity was rare.

CAR T-cell therapy has demonstrated encouraging clinical efficacy and reassuring safety outcomes so far. However, longer prospective studies are needed to assess durability of response, long term safety, factors associated with poor response, and the appropriate selection and timing of patients for therapy.