Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1215939 | ENA |
REPOSITORIES: ENA
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Project description:Oncolytic viruses (OVs) combined with radiotherapy (RT) have shown promise in clinical trials but remain limited by unsatisfactory efficacy. Key challenges include poor intravenous delivery, insufficient RT-induced DNA damage, and suboptimal anti-tumor immune responses. Herein, we developed a novel oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), which incorporates multifunctional polyethyleneimine (PEI)-selenium-PEG (PSSP) to enhance intravenous delivery, viral infectivity, immune response and the efficacy of radiotherapy. The PEGylation shields the virus from rapid clearance, while the ROS-responsive Se-Se bond enables targeted delivery at tumor sites following RT. The exposed PEI enhanced infectivity of AD through electrostatic interactions, consequently augmenting DNA damage after RT via inhibiting the expression of DNA-repair proteins, such as CHEK1 and CDK1. Furthermore, AD-PEI can capture and deliver the RT-induced tumor-released antigens to lymph nodes, thereby activating robust anti-tumor immune responses. Our data from diverse animal models have shown that RadioOnco exhibits unique characteristics, including reversing RT resistance, ability for distant killing, and long-term memory retention, all of which are crucial for addressing metastasis and recurrence in clinical RT. In summary, we have devised an intravenously injectable OVs with synergistic effects in conjunction with RT, achieved through the surface modification of a multifunctional material.
2025-02-02 | PXD060493 |
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.
2025-07-29 | GSE260886 | GEO
Project description:Adoptive T-cell therapy or oncolytic virotherapy has made significant progress, but the efficacy was limited by the lack of infiltration into solid tumors when used alone. Here, an oncolytic virus (rVSV-LCMVG) was designed and combined with adoptively transferred T cells. By turning cold tumors hot, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy, whether rVSV-LCMVG was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and sensitized refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD1, and restoring effector-T cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells, and exhibited comparable amplified anti-tumor effects. This study proposed a rational combination therapy of oncolytic virus with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.
2024-03-15 | GSE235290 | GEO
Project description:Adoptive T-cell therapy or oncolytic virotherapy has made significant progress, but the efficacy was limited by the lack of infiltration into solid tumors when used alone. Here, an oncolytic virus (rVSV-LCMVG) was designed and combined with adoptively transferred T cells. By turning cold tumors hot, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy, whether rVSV-LCMVG was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and sensitized refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD1, and restoring effector-T cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells, and exhibited comparable amplified anti-tumor effects. This study proposed a rational combination therapy of oncolytic virus with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.
2024-03-15 | GSE235289 | GEO
Project description:Radiotherapy (RT) is commonly employed as an adjuvant treatment after surgical resection of osteosarcoma. However, its therapeutic effectiveness is frequently constrained by inadequate radiosensitization and an immunosuppressive tumor microenvironment, which hinders systemic antitumor immune responses and facilitates tumor recurrence and metastasis. In this study, We designed an injectable supermolecular complex of alendronate (Hf-ALN) containing the COX-2 inhibitor celecoxib (CXB), and combined it with radiotherapy to treat osteosarcoma in Balb/c mice. Subsequently, transcriptome analysis was conducted.This injectable radiological immunomodulatory aggregate represents a promising approach that integrates local radiosensitization with immune microenvironment reprogramming to enhance the efficacy of postoperative radiotherapy for osteosarcoma.
2026-09-09 | GSE325820 | GEO
Project description:Interventions: Lung Cancer group:Novel Oncolytic Virus;Colorectal Cancer group:Novel Oncolytic Virus
Primary outcome(s): objective response rate;overall survival;Quality of life;Safety;disease control rate;disease-free survival
Study Design: Single arm
| 2725682 | ecrin-mdr-crc
Project description:Eradication of Solid Human Tumors in Nude Mice with an Intravenously Injected Light-Emitting Oncolytic Vaccinia Virus
| PRJNA101631 | ENA
Project description:Oncolytic HSV-1 derived viruses are being developed for cancer treatment. Here we describe the isolation of a novel strain of HSV-1, and its engineering to safely harness it as an oncolytic therapeutic. This strain (UT1a) was isolated from a de-identified consented patient biorepository. CRISPR-Cas9-based recombination was utilized to insert bacterial artificial chromosome (BAC) genes into the viral UL39 and UL40 locus resulting in the deletion of both large and small subunits of the viral ribonucleotide reductase (RR). Subsequent deletion of viral RL1 genes encoding the neurovirulence factor ɣ34.5, resulted in OncoDelta (OncoD), a virus deleted for UL39, UL40 and both copies of RL1. OncoD retained tumor cell specific cytotoxicity and replication, was safe and non-toxic in intracranial injections in naïve mice up to doses of (5 x 106), maximal injectable dose OncoD and showed significant anti-tumor immune activating potential in multiple tumor models. Transcriptome profiling of OncoD showed that it impaired DNA damage repair pathways and hence synergized with radiation to improve therapeutic response in vitro and in vivo.
2025-04-09 | GSE288846 | GEO
Project description:The oncolytic effect of virotherapy derives from the intrinsic capability of the applied virus in selectively infecting and killing tumor cells. Although oncolytic viruses of various constructions have been shown to efficiently infect and kill tumor cells in vitro, the efficiency of these viruses to exert the same effect on tumor cells within tumor tissues in vivo has not been extensively investigated. Here we report our studies using single-cell RNA sequencing to comprehensively analyze the gene expression profile of tumor tissues following herpes simplex virus 2-based oncolytic virotherapy. Our data revealed the extent and cell types within the tumor microenvironment that could be infected by the virus. Moreover, we observed changes in the expression of cellular genes, including antiviral genes, in response to viral infection. One notable gene found to be upregulated significantly in oncolytic virus-infected tumor cells was Gadd45g, which is desirable for optimal virus replication. These results not only help reveal the precise infection status of the oncolytic virus in vivo, but also provide insight that may lead to the development of new strategies to further enhance the therapeutic efficacy of oncolytic virotherapy.
2021-10-31 | GSE186753 | GEO
Project description:Human melanoma tumor cells (HS294T) and monocytes (THP-1) were infected with a double deleted (-VGF, -TK) oncolytic vaccinia virus expressing human DAI (DNA-dependent activator of interferon-regulatory factors). Total RNA was collected and gene expresson profiles were determined with Agilent microarray. An oncolytic vaccinia virus that does not express DAI was used to control the effect of DAI and uninfected cells (PBS treated) were used to control the effect of virus infection. In oncolytic virotherapy the ability of the virus to activate the immune system against tumors is nowadays generally understood to be a key mechanism in full eradication of cancer and for long-term anti-tumor effects. We armed an oncolytic vaccinia virus with DAI to increase the immunogenicity and the vaccine potency of the virus. The aim of this study was to study if the expression of DAI by a replicating vaccinia virus would alter the gene expression profile of infected cells and to study what are the differentially expressed genes.
2016-03-01 | GSE76208 | GEO