CAR T cells in pediatric systemic lupus erythematosus

Abstract

Pediatric systemic lupus erythematosus (SLE) is associated with high disease severity and significantly higher morbidity and mortality compared to adult-onset SLE, making it a particularly challenging condition to manage. Chimeric antigen receptor (CAR) T-cell therapy holds significant promise for improving outcomes in refractory pediatric SLE. However, the use of CAR T-cell therapy in pediatric patients presents unique challenges, including difficulty in collecting sufficient T cells. Pediatric patients may experience distinct side effects, such as age-specific toxicities or more pronounced neurotoxic events, requiring tailored monitoring and management. Additionally, the psychological impact on children and their families, facing potentially life-threatening treatment protocols, must be carefully addressed. To date, only four children with SLE have been treated with CAR T cells, highlighting the early stage of research in this area. The clinical outcomes provide hope that CAR T-cell therapy could offer a breakthrough in treating pediatric SLE; however, main limitations remain the small number of patients and the relatively short follow-up. More data are needed to fully assess the safety, efficacy, and long-term outcomes in this vulnerable population. Key Points • Pediatric SLE is characterized by more severe manifestations, higher morbidity, and increased mortality compared to adult-onset SLE. • CAR T-cell therapy shows promise as a potential treatment for refractory pediatric SLE aiming ideally towards long-term, drug-free remission. • CAR T-cell therapy in pediatric SLE presents unique challenges, including age-related toxicities, technical difficulties, and ethical considerations. • To date, results are available from only a handful of children with SLE treated with CAR T cells. Expected advancements in CAR T-cell technology, along with data from ongoing clinical trials involving children with SLE, will determine the pace and extent of CAR T-cell therapy application in pediatric SLE.

Keywords: B-cell depletion; CAR T cells; Pediatric lupus; Systemic lupus erythematosus.