儿童脑肿瘤的病毒免疫治疗新兴领域
The emerging field of viroimmunotherapy for pediatric brain tumors
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影响因子:13.4
分区:医学1区 Top / 临床神经病学1区 肿瘤学1区
发表日期:2024 Nov 04
作者:
Marc Garcia-Moure, Virginia Laspidea, Sumit Gupta, Andrew G Gillard, Soumen Khatua, Akhila Parthasarathy, Jiasen He, Frederick F Lang, Juan Fueyo, Marta M Alonso, Candelaria Gomez-Manzano
DOI:
10.1093/neuonc/noae160
摘要
儿童脑肿瘤是儿童中最常见的实体瘤。即使在多模态治疗不断进步的今天，某些类型的肿瘤如儿童型弥漫性高等级胶质瘤或中枢神经系统胚胎瘤的生存率仍然令人失望。对其复杂的分子异质性及肿瘤与微环境相互作用的理解不足，持续阻碍治疗效果的提升。开发一种能改善这些致命性肿瘤存活率的策略仍是儿童神经肿瘤学中的未解之谜。溶瘤病毒（OVs）作为一种可行、安全且有潜力的治疗手段，正在逐渐崭露头角。病毒免疫疗法的新范式认为，病毒的直接细胞毒作用之后，特定条件下会激发抗肿瘤免疫反应，促使肿瘤部分或全部缩小。OVs单独使用或联合其他治疗手段，已主要应用于成人神经肿瘤学。近期在儿童脑肿瘤模型中的前沿临床前研究激增，推动了OVs的临床转化并取得了令人鼓舞的结果。本综述总结了在儿童脑肿瘤中的不同病毒免疫治疗策略及其在临床和前临床研究中的应用，讨论了存在的限制以及未来需要探索的方向，以提升这些肿瘤对该类治疗的反应。© 作者（2024）。由牛津大学出版社代表神经肿瘤学会出版。所有权利保留。如需商业再利用，请联系reprints@oup.com获取复制品和翻译版权。其他权限请通过我们网站上的Permissions链接，使用RightsLink服务申请。如需更多信息，请联系journals.permissions@oup.com。
Abstract
Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the direct cytopathic effect is followed, under certain circumstances, by an antitumor immune response responsible for the partial or complete debulking of the tumor mass. OVs alone or combined with other therapeutic modalities have been primarily used in adult neuro-oncology. A surge in encouraging preclinical studies in pediatric brain tumor models recently led to the clinical translation of OVs with encouraging results in these tumors. In this review, we summarize the different virotherapy tested in preclinical and clinical studies in pediatric brain tumors, and we discuss the limitations and future avenues necessary to improve the response of these tumors to this type of therapy.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.