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Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening.
- Source :
-
Journal of Hematology & Oncology . 5/23/2024, Vol. 17 Issue 1, p1-6. 6p. - Publication Year :
- 2024
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17568722
- Volume :
- 17
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Hematology & Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 177463800
- Full Text :
- https://doi.org/10.1186/s13045-024-01554-5