Malignant brain tumors constitute nearly one-third of cancer diagnoses in children and have recently surpassed hematologic malignancies as the most lethal neoplasm in the pediatric population. Outcomes for children with brain tumors are unacceptably poor and current standards of care—surgical resection, chemotherapy, and radiation—are associated with significant long-term morbidity. Oncolytic virotherapy has emerged as a promising immunotherapy for the treatment of brain tumors. While the majority of brain tumor clinical trials utilizing oncolytic virotherapy have been in adults, five viruses are being tested in pediatric brain tumor clinical trials: herpes simplex virus (G207), reovirus (pelareorep/Reolysin), measles virus (MV-NIS), poliovirus (PVSRIPO), and adenovirus (DNX-2401, AloCELYVIR). Herein, we review past and current pediatric immunovirotherapy brain tumor trials including the relevant preclinical and clinical research that contributed to their development. We describe mechanisms by which the viruses may overcome barriers in treating pediatric brain tumors, examine challenges associated with achieving effective, durable responses, highlight unique aspects and successes of the trials, and discuss future directions of immunovirotherapy research for the treatment of pediatric brain tumors.

恶性脑肿瘤占儿童癌症诊断的近三分之一，最近已超过血液系统恶性肿瘤，成为儿科人群中最致命的肿瘤。患有脑肿瘤的儿童的预后差得令人无法接受，目前的护理标准——手术切除、化疗和放疗——与显着的长期发病率有关。溶瘤病毒疗法已成为治疗脑肿瘤的一种有前途的免疫疗法。虽然大多数利用溶瘤病毒疗法的脑肿瘤临床试验都是在成人中进行的，但有五种病毒正在儿童脑肿瘤临床试验中进行测试：单纯疱疹病毒 (G207)、呼肠孤病毒 (pelareorep/Reolysin)、麻疹病毒 (MV-NIS)、脊髓灰质炎病毒 (PVSRIPO) 和腺病毒 (DNX-2401, AloCELYVIR)。在此处，我们回顾了过去和当前的儿科免疫病毒治疗脑肿瘤试验，包括促进其发展的相关临床前和临床研究。我们描述了病毒可能克服治疗小儿脑肿瘤障碍的机制，检查与实现有效、持久反应相关的挑战，强调试验的独特方面和成功，并讨论免疫病毒疗法研究治疗小儿脑肿瘤的未来方向。