溶瘤病毒
胶质母细胞瘤
免疫系统
肿瘤细胞
病毒
癌症研究
医学
脑瘤
免疫学
生物
病理
作者
Zheng Yang,Xiaomin Wang,Qiang Ji,Aizhong Fang,Lairong Song,Xiaoying Xu,Yi Lin,Peng Yue,Jianyu Yu,Lei Xie,Feng Chen,Xiaojie Li,Sipeng Zhu,Botao Zhang,Lili Zhou,Chunna Yu,Yali Wang,Liang Wang,Han Hwa Hu,Ziyi Zhang,Binlei Liu,Zhen Wu,Wenbin Li
标识
DOI:10.1016/j.canlet.2024.216834
摘要
Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.
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