Abstract
Chimeric Antigen Receptor (CAR) T cell therapy has recently begun to be used for solid tumors such as glioblastoma multiforme. Many children with pediatric malignant brain tumors develop extensive long-term morbidity of intensive multimodal curative treatment. Others with certain diagnoses and relapsed disease continue to have limited therapies and a dismal prognosis. Novel treatments such as CAR T cells could potentially improve outcomes and ameliorate the toxicity of current treatment. In this review, we discuss the potential of using CAR therapy for pediatric brain tumors. The emerging insights on the molecular subtypes and tumor microenvironment of these tumors provide avenues to devise strategies for CAR T cell therapy. Unique characteristics of these brain tumors, such as location and associated morbid treatment induced neuro-inflammation, are novel challenges not commonly encountered in adult brain tumors. Despite these considerations, CAR T cell therapy has the potential to be integrated into treatment schema for aggressive pediatric malignant brain tumors in the future.
Highlights
Chimeric antigen receptor (CAR) T cells are a form of adoptive cell therapy used for immunotherapy
We focus on pediatric brain tumors as novel interventions are needed given the grim prognoses for many patients
Ahmed et al showed a dramatic response in an adolescent patient, and stable disease in 7 others after HER2 CAR-T infusion [132]
Summary
Chimeric antigen receptor (CAR) T cells are a form of adoptive cell therapy used for immunotherapy. Antigenic Targets Studies have demonstrated increased expression of EphA2, IL13Rα2, HER2 and Survivin in ependymomas [77, 78] These antigens may be potentially effective targets in CAR T cell mediated therapy clinically. Macrophages predominantly infiltrate the ATRT-SHH and ATRT-MYC subtypes and correlate with poor prognosis and treatment resistance [109] These data again indicate that therapeutic strategies must take into account the subtype classification and its respective immune microenvironment properties in pediatric brain tumors. A recently published study demonstrated the potent antitumorgenic capabilities of CAR-T cells targeted to pediatric diffuse midline gliomas [138] In these tumors, the presence of the H3-K27M mutation correlated with high levels of GD2 diganglioside expression. These risks may occur more frequently as the clinical experience expands in pediatric brain tumors
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