Oncolytic viruses, such as oncolytic herpes simplex virus (oHSV), are a new class of cancer therapeutic, which selectively replicate and kill cancer cells, while inducing an inflammatory microenvironment, immunovirotherapy. Recently, an oHSV (talimogene laherparepvec) has been approved for the treatment of advanced melanoma. Glioblastoma (GBM) is an almost always lethal primary tumor in the brain that is highly immunosuppressive, and posited to contain GBM stem-like cells (GSCs). Immune checkpoint blockade has revolutionized therapy for some cancers, but not GBM. We have used a syngeneic GSC-derived orthotopic GBM model (005) to develop immunotherapeutic strategies. Curative therapy required oHSV expressing IL-12 in combination with two checkpoint inhibitors, anti-PD-1 and anti-CTLA-4. This response required CD4 and CD8 T cells, and macrophages in a complex interplay.
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| http://dx.doi.org/10.2217/imt-2018-0009 | DOI Listing |
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Blocking feedback immunosuppression of antigen presentation in brain tumor during oncolytic virotherapy with oHSV-mshPKR.
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Augusta University, Augusta, Georgia, United States.
Glioblastoma (GBM) is the most frequent malignant brain tumor. We recently discovered that oncolytic herpes simplex virus engineered to disable tumor-intrinsic protein kinase R (PKR) signaling (oHSV-shPKR) could increase oHSV oncolysis and anti-tumor immune response. However, here we show that disabling tumor-intrinsic PKR signaling can also induce the activation of the indoleamine 2,3-dioxygenase (IDO) signaling pathway.
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Department of Neurological Surgery, the University of Alabama at Birmingham, Birmingham, AL, USA.
The authors present a comprehensive review on the history and development of oncolytic herpes simplex viral therapies for malignant glioma with a focus on mechanisms of delivery in prior and ongoing clinical trials. This review highlights the advancements made with regard to delivering these therapies to a highly complex immunologic environment in the setting of the blood brain and blood tumor barrier in a safe and effective manner.
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[Construction of a stable 4T1 cell line expressing by the PiggyBac transposon system].
Sheng Wu Gong Cheng Xue Bao
November 2024
School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, Hubei, China.
To investigate the mechanism of the major capsid protein VP5 (encoded by the gene) of oncolytic herpes simplex virus type Ⅱ (oHSV2) in regulating the antitumor function of immune cells, we constructed a mouse breast cancer cell line 4T1-iRFP-VP5-GFP stably expressing VP5 protein, near-infrared fluorescent protein (iRFP), and green fluorescent protein (GFP) by using the PiggyBac transposon system. Flow cytometry and Western blotting were employed to screen the monoclonal cell lines expressing both GFP and VP5 and examine the expression stability of in the constructed cell line. The results of SYBR Green I real-time PCR and Western blotting showed that the copies of and the expression level of VP5 protein in the 15th passage of 4T1-iRFP-VP5-GFP cells were significantly higher than those in the 4T1 cells transiently transfected with , demonstrating the stable insertion of into the 4T1 cell genome.
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