Abstract
Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogeneous antigen expression, limited infiltration of T cells into the tumour, the selective trafficking provided by the blood–brain barrier, and the immunosuppressive tumour microenvironment have emerged as the main hurdles that need to be overcome for the success of CAR T cell therapy. In this review, we will focus mainly on the characteristics of the deadliest high-grade CNS paediatric tumours (medulloblastoma, ependymoma, and high-grade gliomas) and the potential of CAR T cell therapy to increase survival and patients’ quality of life.
Highlights
Central nervous system (CNS) tumours are the most common solid cancers in childhood, as well as the leading cause of cancer-related death in children
Paediatric brain tumours represent a challenge for successful immunotherapy treatment. They possess unique characteristics, including low mutational burden, tumour heterogeneity that leads to tumour evasion, location, the barrier generated by the brain–blood barrier (BBB), the immunosuppressive tumour microenvironment (TME), and the treatment-related toxicities that may cause fatal consequences on the CNS [10]
Optimisation of the chimeric antigen receptor T (CAR T) cell manufacturing process to enrich for the population, which can contribute to sustaining an effective antitumour response, is crucial, especially when they encounter hostile conditions of solid tumours [167,182]
Summary
Central nervous system (CNS) tumours are the most common solid cancers in childhood, as well as the leading cause of cancer-related death in children. Even the cure is paid at a high price; the adverse effects of current treatments on the developing brain leave these children with long-term dramatic sequelae. Their quality of life is drastically affected by neurologic irreversible effects, endocrine disease, cognitive and developmental disorders, and the possibility of generating secondary malignancies [4]. Paediatric brain tumours represent a challenge for successful immunotherapy treatment They possess unique characteristics, including low mutational burden, tumour heterogeneity that leads to tumour evasion, location, the barrier generated by the BBB, the immunosuppressive TME, and the treatment-related toxicities that may cause fatal consequences on the CNS [10]. We are going to discuss the potential strategies to overcome these hurdles
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