| Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening | |
| 論文作者 | Zhong, YY; Le, HY; Zhang, X; Dai, Y; Guo, F; Ran, XJ; Hu, GH; Xie, Q; Wang, DW; Cai, YJ |
| 期刊/會(huì)議名稱 | JOURNAL OF HEMATOLOGY & ONCOLOGY |
| 論文年度 | 2024 |
| 論文類別 | |
| 摘要 | Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening. In models of glioblastoma (GBM) and triple-negative breast cancer (TNBC), we showed that the combination of OV and a PARP inhibitor (PARPi) exhibited superior efficacy compared to either monotherapy. Additionally, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy sensitized TNBC to immune checkpoint blockade, and the incorporation of an immune checkpoint inhibitor (ICI) further increased the survival rate of tumor-bearing mice. The combination of PARPi and ICI synergistically enhanced the ability of OV to establish durable tumor-specific immune responses. Our study effectively overcomes the inherent limitations of OV therapy, providing valuable insights for the clinical treatment of TNBC, GBM, and other malignancies. |
| 期 | 1 |
| 卷 | 17 |
| 影響因子 | 29.5 |
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