Project description:Prostate cancer is a major challenge due to limited treatment options in advanced stages. Immunotherapy has shown promising prospects in various cancers, but it faces obstacles in prostate cancer due to its immunosuppressive microenvironment and low response rate to current therapies. Oncolytic virus therapy provides a new immunotherapy approach by stimulating anti-tumor immune responses. This study investigated the histological changes of the novel herpes simplex virus type II (HSV-II) oncolytic virus OH2 in prostate cancer tumors.
Project description:Prostate cancer is a major challenge due to limited treatment options in advanced stages. Immunotherapy has shown promising prospects in various cancers, but it faces obstacles in prostate cancer due to its immunosuppressive microenvironment and low response rate to current therapies. Oncolytic virus therapy provides a new immunotherapy approach by stimulating anti-tumor immune responses. This study investigated the histological changes of the novel herpes simplex virus type II (HSV-II) oncolytic virus OH2 in prostate cancer tumors.
Project description:Prostate cancer is a major challenge due to limited treatment options in advanced stages. Immunotherapy has shown promising prospects in various cancers, but it faces obstacles in prostate cancer due to its immunosuppressive microenvironment and low response rate to current therapies. Oncolytic virus therapy provides a new immunotherapy approach by stimulating anti-tumor immune responses. This study investigated the histological changes of the novel herpes simplex virus type II (HSV-II) oncolytic virus OH2 in prostate cancer tumors.
Project description:Prostate cancer is a major challenge due to limited treatment options in advanced stages. Immunotherapy has shown promising prospects in various cancers, but it faces obstacles in prostate cancer due to its immunosuppressive microenvironment and low response rate to current therapies. Oncolytic virus therapy provides a new immunotherapy approach by stimulating anti-tumor immune responses. This study investigated the histological changes of the novel herpes simplex virus type II (HSV-II) oncolytic virus OH2 in prostate cancer tumors.
Project description:The formation of TLSs induced by oncolytic virus treatment can enhance the anti-tumor response of oral cancer. Therefore, oncolytic virotherapy in vivo is a good strategy. To understand the mechanism of post-treatment changes, we collected oHSV-treated tumors for RNA-seq.
Project description:The paper describes a model of oncolytic virotherapy.
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This model is described in the article:
Mathematical Modelling of the Interaction Between Cancer Cells and an Oncolytic Virus: Insights into the Effects of Treatment Protocols
Adrianne L. Jenner, Chae-Ok Yun, Peter S. Kim, Adelle C. F. Coster
Bull Math Biol (2018) 80:1615–1629
Abstract:
Oncolyticvirotherapyisanexperimentalcancertreatmentthatusesgenet- ically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity Kim et al. (Biomaterials 32(9):2314–2326, 2011) modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. Whilst PEG mod- ification appeared to improve plasma retention and initial infectivity, it also increased the virus particle arrival time. We derive a mathematical model that describes the inter- action between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations, we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy are explored.
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Project description:Oncolytic rhabdoviruses are being evaluated clinically for the treatment of cancer . In this study, we observed that several microtubule-destabilizing agents, sensitize cancer cells to oncolytic rhabdoviruses. To further understand the mechanism of action, we performed microarray analysis of 786-0 tumor cells before and after treatment with both colchcine(100nM) and VSVd51-GFP (MOI=0.01). Go-Term analysis of this dataset revealed that activation of the type I interferon (IFN) response against the VSVd51-GFP virus appears to be inhbitted by colchcine, but not the first wave of type I IFN mRNA transcription.
Project description:To investigate the impact of the tumor microenvironment on fibroblast succeptibility to oncolytic virus infection, we treated normal and cancer-associatted fibrboblasts isolated from the same lung carcinoma patient with the oncolytic virus VSVd51. Birefly, 1E6 cells of both types were seeded in a 6 well dish to allow adherence overnight. The following day, cells were treated with VSV?51 at an MOI=0.01 or left untreated. Eighteen hours following treatment, total RNA was extracted using an RNAeasykit (Qiagen Inc., Valencia, CA) according to the manufactureM-^Rs protocol and triplicate samples were pooled prior to hybridization. Sample quality was verified on abioanalyzer (Agilent Technologies), processed and hybridized to a GeneChip Human Gene 1.0 ST Array according to manufacturer instructions
Project description:Viral oncolysis is supposed to be a promising cancer treatment method because of its good tolerability and durable anti-tumor effects. Compared with other oncolytic viruses, newcastle disease virus (NDV) has some distinct advantages, namely, NDV is a RNA virus which can not recombine with the host genome, making it safer compared to DNA viruses and retroviruses; NDV can induce syncytium formation, allowing the virus to spread between cells without exposure to host neutralizing antibodies; because of hexamer genetic code rule, NDV genome has an lower rate of gene recombination and higher genetic stability. This study systematically investigates the oncolytic mechanism of NDV against colonic carcinoma on transcriptional level and provides theoretical foundations for developing NDV-based therapies targeting colon cancer.
Project description:Glioblastoma multiforme (GBM) treatment is a persistent challenge for oncologists, and this challenge has motivated the exploration of novel therapeutic strategies such as oncolytic virus therapy. Despite recent advancements in oncolytic virus therapy clinical trials for glioblastoma, a substantial number of patients have shown limited responses to this treatment. Here, we performed CRISPR‒Cas9 knockout screening and identified non-canonical BRG1/BRM-associated factor (ncBAF) complex as a pivotal determinant of oncolytic virus resistance. Knockout of the ncBAF-specific subunit Bromodomain-containing protein 9 (BRD9) markedly augmented the antitumor efficacy of oncolytic herpes simplex virus type 1 (oHSV1), as evidenced by our in vitro and in vivo studies. Mechanistically, BRD9 bound to RELA, a key transcription factor in the nuclear factor-κB (NF-κB) signaling pathway, to potentiate the expression of downstream antiviral genes. The application of a small molecule inhibitor targeting BRD9 (IBRD9) significantly enhanced oHSV1 activity against GBM across various models, including cell lines, patient-derived organoids, ex vivo cultured primary tumor slices, and mouse models. Moreover, reduced BRD9 levels correlated with improved patient outcomes in oHSV1 clinical trials. These findings highlight BRD9 as a prospective target for augmenting the effectiveness of oncolytic virus therapy against glioblastoma, providing insights for the development of novel combination treatments.