Glioblastoma（GB）是一种恶性且免疫抑制的脑癌，尽管目前的标准治疗仍无法治愈。放射治疗是治疗GB的主要方法，但位于辐射区外的侵入性癌细胞和放射性抗性使得无法完全清除GB细胞。基于瘤选择性的病毒治疗利用能够在肿瘤内部传播并摧毁肿瘤的病毒，同时刺激抗肿瘤免疫反应，因此有望在放疗后使用。我们证明了病毒溶液-4L溶液-2R天花病毒（VACV）基于病毒选择性和肿瘤细胞浸润的能力，可以在体外复制和引起放疗后的脑肿瘤干细胞细胞毒活性。更重要的是，单一的10Gy剂量的辐射结合溶液-4L溶液-2R VACV与单一治疗相比，对免疫竞争性正交CT2A-luc小鼠模型的治疗效果显著改善，极大地延长生存时间，整治大部分小鼠有了积极的效果。组合治疗后可以使治愈的小鼠在颅内肿瘤的挑战后相对于与年龄相配的小鼠显示出明显增加的生存率，并具有一些完全的排斥。此外，与单一治疗相比，该组合疗法与CD8+效应T细胞和调节性T细胞的比值增加相关。这项研究验证了与基于病毒选择性的病毒治疗一起使用放射治疗的有效性，从而改善了这种恶性脑癌的治疗效果。版权所有©2023，由Elsevier B.V.出版。

Glioblastoma (GB) is a malignant and immune-suppressed brain cancer that remains incurable despite the current standard of care. Radiotherapy is a mainstay of GB treatment, however invasive cancer cells outside the irradiated field and radioresistance preclude complete eradication of GB cells. Oncolytic virus therapy harnesses tumor-selective viruses to spread through and destroy tumors while stimulating antitumor immune responses, and thus has potential for use following radiotherapy. We demonstrate that oncolytic ΔF4LΔJ2R vaccinia virus (VACV) replicates in and induces cytotoxicity of irradiated brain tumor initiating cells in vitro. Importantly, a single 10 Gy dose of radiation combined with ΔF4LΔJ2R VACV produced considerably superior anticancer effects relative to either monotherapy when treating immune-competent orthotopic CT2A-luc mouse models-significantly extending survival and curing the majority of mice. Mice cured by the combination displayed significantly increased survival relative to naïve age-matched controls following intracranial tumor challenge, with some complete rejections. Further, the combination therapy was associated with an increased ratio of CD8+ effector T cells to regulatory T cells compared to either monotherapy. This study validates the use of radiation with an oncolytic ΔF4LΔJ2R VACV to improve treatment of this malignant brain cancer.Copyright © 2023. Published by Elsevier B.V.