Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Cancer Metastasis Rev. 2024 Dec;43(4):1205-1216. doi: 10.1007/s10555-024-10208-4. Epub 2024 Sep 9.
Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited. Furthermore, for diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG), there are currently no curative therapies. Chimeric antigen receptor T (CAR T) cell therapy is a promising novel treatment avenue for these tumors. Here, we review the preclinical evidence for CAR T cell use in pediatric brain tumors, the preliminary clinical experience of CNS CAR T cell trials, toxicity associated with systemic and locoregional CAR T cell therapy for CNS tumors, challenges in disease response evaluation with CAR T cell therapy, and the knowledge gained from correlative biologic studies from these trials in the pediatric and young adult population.
中枢神经系统（CNS）肿瘤是儿童癌症相关死亡的主要原因。儿童 CNS 肿瘤的典型治疗方法包括手术、放疗和化疗的综合应用。虽然前期治疗对许多高级别肿瘤有效，但复发时的治疗仍然有限。此外，对于弥漫性内在脑桥胶质瘤（DIPG）和弥漫性中线胶质瘤（DMG），目前尚无治愈疗法。嵌合抗原受体 T（CAR T）细胞疗法是这些肿瘤的一种很有前途的新治疗途径。在这里，我们回顾了 CAR T 细胞在儿科脑肿瘤中的临床前应用证据、CNS CAR T 细胞试验的初步临床经验、全身和局部 CAR T 细胞治疗 CNS 肿瘤相关的毒性、CAR T 细胞治疗中疾病反应评估的挑战，以及从儿科和年轻成人人群中这些试验的相关生物学研究中获得的知识。
