Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, Universidad de Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, C/Irunlarrea 3, 31008 Pamplona, Spain.
Pediatric Onco-Hematology Unit, Hospital Universitario Virgen Macarena, School of Medicine, Universidad de Sevilla, Avenida Dr, Fedriani 3, 41009 Sevilla, Spain; Sociedad Española de Hematología y Oncología Pediátricas (SEHOP), Spain.
J Control Release. 2022 Aug;348:553-571. doi: 10.1016/j.jconrel.2022.06.010. Epub 2022 Jun 17.
Embryonal tumors of the nervous system are neoplasms predominantly affecting the pediatric population. Among the most common and aggressive ones are neuroblastoma (NB) and medulloblastoma (MB). NB is a sympathetic nervous system tumor, which is the most frequent extracranial solid pediatric cancer, usually detected in children under two. MB originates in the cerebellum and is one of the most lethal brain tumors in early childhood. Their tumorigenesis presents some similarities and both tumors often have treatment resistances and poor prognosis. High-risk (HR) patients require high dose chemotherapy cocktails associated with acute and long-term toxicities. Nanomedicine and cell therapy arise as potential solutions to improve the prognosis and quality of life of children suffering from these tumors. Indeed, nanomedicines have been demonstrated to efficiently reduce drug toxicity and improve drug efficacy. Moreover, these systems have been extensively studied in cancer research over the last few decades and an increasing number of anticancer nanocarriers for adult cancer treatment has reached the clinic. Among cell-based strategies, the clinically most advanced approach is chimeric-antigen receptor (CAR) T therapy for both pathologies, which is currently under investigation in phase I/II clinical trials. However, pediatric drug research is especially hampered due not only to ethical issues but also to the lack of efficient pre-clinical models and the inadequate design of clinical trials. This review provides an update on progress in the treatment of the main embryonal tumors of the nervous system using nanotechnology and cell-based therapies and discusses key issues behind the gap between preclinical studies and clinical trials in this specific area. Some directions to improve their translation into clinical practice and foster their development are also provided.
神经母细胞瘤和髓母细胞瘤是儿童中最常见和最具侵袭性的胚胎性肿瘤。神经母细胞瘤（NB）是一种交感神经系统肿瘤，是最常见的儿童颅外实体瘤，通常在两岁以下的儿童中发现。髓母细胞瘤起源于小脑，是儿童早期最致命的脑肿瘤之一。它们的肿瘤发生存在一些相似之处，两种肿瘤通常都有治疗抵抗和预后不良的问题。高危（HR）患者需要高剂量的化疗药物联合急性和长期毒性。纳米医学和细胞疗法作为提高患有这些肿瘤的儿童预后和生活质量的潜在解决方案而出现。实际上，纳米药物已被证明可以有效地降低药物毒性并提高药物疗效。此外，这些系统在过去几十年的癌症研究中得到了广泛的研究，越来越多的用于成人癌症治疗的抗癌纳米载体已进入临床阶段。在基于细胞的策略中，最先进的临床方法是针对这两种疾病的嵌合抗原受体（CAR）T 疗法，目前正在 I/II 期临床试验中进行研究。然而，儿科药物研究受到阻碍，不仅是因为伦理问题，还因为缺乏有效的临床前模型和临床试验设计不当。本文综述了使用纳米技术和基于细胞的疗法治疗主要的神经母细胞瘤的最新进展，并讨论了这一特定领域中临床前研究与临床试验之间差距背后的关键问题。还提供了一些改善其转化为临床实践和促进其发展的方向。
