Tumor-targeting oncolytic viruses engineered for glioblastoma immunotherapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE244034 | GEO | 2025/07/14
REPOSITORIES: GEO
Similar Datasets
Project description:Tumor-targeting oncolytic viruses engineered for glioblastoma immunotherapy
| PRJNA1021139 | ENA
Project description:Oncolytic biomineralized bacteria for tumor immunotherapy
| PRJNA868767 | ENA
Project description:Bacteria-based cancer immunotherapy, dated back to Coley’s toxins (inactivated bacteria) in 1893, has recently regained substantial attentions, usually by using attenuated bacteria to transform immune-silent “cold” tumors into immune-inflamed “hot” ones. However, while inactivated bacteria showed limited antitumor efficacy, attenuated live bacteria often possessed significant safety risks. Herein, by biomineralizing growth of manganese dioxide on the surface of paraformaldehyde-fixed gram-negative Salmonella typhimurium (S. typhimurium), we obtained MnO2-coated fixed S. typhimurium (M@F.S), which showed potent immune-stimulating effects via activating multiple pathways including Toll-like receptors (TLRs), cyclic GMP-AMP Synthase (cGAS)-stimulator of interferon genes (STING) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). Single intratumoral administration of M@F.S at safe doses resulted in surprisingly strong efficacies in suppressing various types of mouse tumor models and a rabbit cancer model, and the cured mice and rabbits gained immune memory to reject re-challenged tumors. An abscopal antitumor effect was also observed, suggesting systemic antitumor immunity triggered by local injection of M@F.S. The antitumor mechanisms of M@F.S were preliminarily demonstrated to be innate immune activation initiated by multiple signaling pathways, followed by subsequent activation of tumor-specific immune responses, together with the modulation of immunosuppressive tumor microenvironment. We further demonstrated the efficacy of biomineralized bacteria in inhibiting an orthotopic breast tumor model established on tree shrews, an alternative animal model to primates with better clinical relevance. Such oncolytic biomineralized bacteria could be a potent yet safe immunotherapeutic agent for treatment of various solid tumors.
2024-08-01 | GSE211069 | GEO
Project description:We found that overexpression of APOA1 in glioblastoma (GBM) promotes cholesterol efflux from TAMs and restores phagocytosis and antigen presentation. Therefore, we constructed a recombinant oncolytic adenovirus expressing APOA1 to carry the cholesterol regulatory elements of TAMs. AdV-APOA1 exhibited better antitumor effects than AdV-Ctrl in several orthotopic GBM tumor models. Further, we collected virus-treated GL261-CAR tumors for RNA-seq to reveal differences in biological processes between them. Specifically, intracranial 14-day GL261-CAR-bearing C57BL/6J mice were i.t. injected with 1 × 108 PFU AdV-Ctrl or 1 × 108 PFU AdV-APOA1. The tumor bulks were then collected to perform transcriptome RNA-seq analysis 3 days after virus injection.
2022-05-04 | GSE201976 | GEO
Project description:In this study we demonstrate the effect of oncolytic adenoviruses armed with CXCL9, CXCL10 and IL-15 to infect cancer cells, secrete the encoded protein and drive gradient-dependent T-cell attraction. Our in vivo validation demonstrated an increased intratumoral CD4+ and CD8+ T-cell infiltration following treatment with armed viruses compared to control groups. Finally, RCC cells were screened for tumor-specific peptides to validate their immunogenicity in a (personalized) oncolytic cancer vaccine approach, previously referred to as PeptiCRAd.
2025-05-06 | PXD051880 | Pride
Project description:We explored the utility of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile Virus (WNV) indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a murine adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs, and thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.
2017-08-23 | GSE102244 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to enhance tumor tropism and glioma-selective replication. E1A mutant adenovirus Delta-24-RGD has shown favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of cytosolic, nuclear, and secreted glioma proteomes throughout the early time course of Delta-24-RGD infection.
2018-10-22 | PXD008022 | Pride
Project description:Regional delivery of oncolytic viruses has been shown to promote immune responses. Malignant pleural effusions comprise an immunosuppressive microenvironment, and the ability of oncolytic viruses to generate immune responses following regional delivery in patients with malignant pleural effusions is unknown. We conducted a phase I clinical trial that studied the intrapleural administration of oncolytic vaccinia virus to establish the safety and feasibility in patients with malignant pleural effusion due to malignant pleural mesothelioma or metastatic disease. In patients with malignant pleural mesothelioma, by correlative analysis of pre- and post-treatment tumor biopsies, we provide insight into tumor-specific viral uptake and associated immune responses.
2023-01-27 | GSE223395 | GEO
Project description:By their selective infection or replication into tumors, oncolytic viruses trigger profound modifications of tumor immune microenvironment with a massive infiltration and activation of T cells. This tumor warming up can be further amplified by the local delivery of powerful immunomodulatory molecules encoded into virus’ genome. Those properties are particularly of interest for tumor poorly infiltrated or infiltrated with anergic T cells to reverse patient’s unresponsiveness to immune checkpoint inhibitors (ICI). TG6050 is a new oncolytic vaccinia virus encoding single-chain human Interleukin-12 (hIL-12) and full length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. Replication, oncolysis, selectivity, transgenes expression and functionality of TG6050 were characterized in vitro. Virus and IL-12 pharmacokinetics, antitumoral activities (alone or combined with ICI), and mechanism of action (MOA) were investigated in “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. MOA was deciphered by monitoring both systemic and tumor immune responses, and tumor transcriptome analyses. Finally, TG6050 safety after repeated intravenous administrations was evaluated in cynomolgus monkeys and special attention was paid to the level of circulating IL-12 potentially associated with toxic effects. In vitro or in vivo replication of TG6050 in tumor cells allows local expression of functional IL-12 and @CTLA-4. The expression of transgenes, together with the virus replication, translated into an antitumoral activity in both “cold and “hot” tumor murine models that was further amplified by combination with ICI. Analysis of tumor microenvironment (TME) after TG6050 treatment showed an increase of interferon gamma, CD8+ T cells, M1/M2 macrophages ratio and a drastic decrease of regulatory T cells. Those local modifications were observed together with an enhanced systemic and specific antitumor adaptive immune response. In toxicology studies, the virus did not produce any observable adverse effects in cynomolgus monkeys. Conclusions: TG6050 allows the delivery of functional IL-12 and @CTLA-4 into tumor resulting in an excellent antitumor activity along with a shift towards an inflamed TME, and a boost of the systemic antitumor T-cells. Toxicological studies in macaques demonstrated the safety of TG6050. Together these results paved the way for clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926).
2024-07-30 | GSE259380 | GEO
Project description:By their selective infection or replication into tumors, oncolytic viruses trigger profound modifications of tumor immune microenvironment with a massive infiltration and activation of T cells. This tumor warming up can be further amplified by the local delivery of powerful immunomodulatory molecules encoded into virus’ genome. Those properties are particularly of interest for tumor poorly infiltrated or infiltrated with anergic T cells to reverse patient’s unresponsiveness to immune checkpoint inhibitors (ICI). TG6050 is a new oncolytic vaccinia virus encoding single-chain human Interleukin-12 (hIL-12) and full length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. Replication, oncolysis, selectivity, transgenes expression and functionality of TG6050 were characterized in vitro. Virus and IL-12 pharmacokinetics, antitumoral activities (alone or combined with ICI), and mechanism of action (MOA) were investigated in “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. MOA was deciphered by monitoring both systemic and tumor immune responses, and tumor transcriptome analyses. Finally, TG6050 safety after repeated intravenous administrations was evaluated in cynomolgus monkeys and special attention was paid to the level of circulating IL-12 potentially associated with toxic effects. In vitro or in vivo replication of TG6050 in tumor cells allows local expression of functional IL-12 and @CTLA-4. The expression of transgenes, together with the virus replication, translated into an antitumoral activity in both “cold and “hot” tumor murine models that was further amplified by combination with ICI. Analysis of tumor microenvironment (TME) after TG6050 treatment showed an increase of interferon gamma, CD8+ T cells, M1/M2 macrophages ratio and a drastic decrease of regulatory T cells. Those local modifications were observed together with an enhanced systemic and specific antitumor adaptive immune response. In toxicology studies, the virus did not produce any observable adverse effects in cynomolgus monkeys. Conclusions: TG6050 allows the delivery of functional IL-12 and @CTLA-4 into tumor resulting in an excellent antitumor activity along with a shift towards an inflamed TME, and a boost of the systemic antitumor T-cells. Toxicological studies in macaques demonstrated the safety of TG6050. Together these results paved the way for clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926).
2024-07-30 | GSE259379 | GEO