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Advances and potential pitfalls of oncolytic viruses expressing immunomodulatory transgene therapy for malignant gliomas.
Cell Death & Disease ( IF 9 ) Pub Date : 2020-06-25 , DOI: 10.1038/s41419-020-2696-5
Qing Zhang 1, 2, 3 , Fusheng Liu 1, 2, 3
Affiliation  

Glioblastoma (GBM) is an immunosuppressive, lethal brain tumor. Despite advances in molecular understanding and therapies, the clinical benefits have remained limited, and the life expectancy of patients with GBM has only been extended to ~15 months. Currently, genetically modified oncolytic viruses (OV) that express immunomodulatory transgenes constitute a research hot spot in the field of glioma treatment. An oncolytic virus is designed to selectively target, infect, and replicate in tumor cells while sparing normal tissues. Moreover, many studies have shown therapeutic advantages, and recent clinical trials have demonstrated the safety and efficacy of their usage. However, the therapeutic efficacy of oncolytic viruses alone is limited, while oncolytic viruses expressing immunomodulatory transgenes are more potent inducers of immunity and enhance immune cell-mediated antitumor immune responses in GBM. An increasing number of basic studies on oncolytic viruses encoding immunomodulatory transgene therapy for malignant gliomas have yielded beneficial outcomes. Oncolytic viruses that are armed with immunomodulatory transgenes remain promising as a therapy against malignant gliomas and will undoubtedly provide new insights into possible clinical uses or strategies. In this review, we summarize the research advances related to oncolytic viruses that express immunomodulatory transgenes, as well as potential treatment pitfalls in patients with malignant gliomas.



中文翻译:

表达免疫调节转基因治疗恶性神经胶质瘤的溶瘤病毒的进展和潜在缺陷。

胶质母细胞瘤(GBM)是一种免疫抑制性致命脑肿瘤。尽管分子认识和治疗取得了进步,但临床获益仍然有限,GBM 患者的预期寿命仅延长至约 15 个月。目前,表达免疫调节转基因的转基因溶瘤病毒(OV)构成了胶质瘤治疗领域的研究热点。溶瘤病毒旨在选择性地靶向、感染肿瘤细胞并在肿瘤细胞中复制,同时不伤害正常组织。此外,许多研究已经显示出治疗优势,最近的临床试验也证明了其使用的安全性和有效性。然而,单独的溶瘤病毒的治疗功效是有限的,而表达免疫调节转基因的溶瘤病毒是更有效的免疫诱导剂,并增强 GBM 中免疫细胞介导的抗肿瘤免疫反应。越来越多的关于编码恶性胶质瘤免疫调节转基因疗法的溶瘤病毒的基础研究已经取得了有益的结果。携带免疫调节转基因的溶瘤病毒作为恶性神经胶质瘤的治疗方法仍然很有前景,并且无疑将为可能的临床用途或策略提供新的见解。在这篇综述中,我们总结了与表达免疫调节转基因的溶瘤病毒相关的研究进展,以及恶性胶质瘤患者的潜在治疗陷阱。

更新日期:2020-06-25
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