Spatial transcriptomics reveals the immunomodulatory activities of an oncolytic adenovirus armed with a type I interferon in a replication-permissive immunocompetent pancreatic cancer model
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ORGANISM(S): Mesocricetus auratus
PROVIDER: GSE286008 | GEO | 2025/01/14
REPOSITORIES: GEO
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Project description:Spatial transcriptomics reveals the immunomodulatory activities of an oncolytic adenovirus armed with a type I interferon in a replication-permissive immunocompetent pancreatic cancer model
| PRJNA1207477 | ENA
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:Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. This is partly attributable to the immunosuppressive microenvironment of liver metastases, which inhibits immune activation. To unleash anti-tumoral immune responses against liver metastases, we armed liver and tumor-associated macrophages to coordinately express tumor antigens (TAs), IFNα and IL-12. The combination of TAs with both cytokines yielded the most potent therapeutic response, resulting in the eradication of established liver metastases in several mouse models of the disease. Mechanistically, armed macrophages expanded tumor reactive CD8+ T cells, which in the presence of IFNα and IL-12 acquired features of progenitor exhausted T cells and killed cancer cells independently of CD4+ T cell help. IFNα and IL-12 produced within the liver tissue by armed macrophages rewired cell interactions within the tumor microenvironment and reprogrammed antigen presenting cells to further support T cell effector functions. Tumor reactive T cell rejuvenation and strong therapeutic activity were observed in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring private neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages expressing TA and immune-activating cytokines to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
2025-03-10 | GSE273611 | GEO
Project description:Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. This is partly attributable to the immunosuppressive microenvironment of liver metastases, which inhibits immune activation. To unleash anti-tumoral immune responses against liver metastases, we armed liver and tumor-associated macrophages to coordinately express tumor antigens (TAs), IFNα and IL-12. The combination of TAs with both cytokines yielded the most potent therapeutic response, resulting in the eradication of established liver metastases in several mouse models of the disease. Mechanistically, armed macrophages expanded tumor reactive CD8+ T cells, which in the presence of IFNα and IL-12 acquired features of progenitor exhausted T cells and killed cancer cells independently of CD4+ T cell help. IFNα and IL-12 produced within the liver tissue by armed macrophages rewired cell interactions within the tumor microenvironment and reprogrammed antigen presenting cells to further support T cell effector functions. Tumor reactive T cell rejuvenation and strong therapeutic activity were observed in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring private neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages expressing TA and immune-activating cytokines to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
2025-03-10 | GSE273610 | GEO
Project description:Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. This is partly attributable to the immunosuppressive microenvironment of liver metastases, which inhibits immune activation. To unleash anti-tumoral immune responses against liver metastases, we armed liver and tumor-associated macrophages to coordinately express tumor antigens (TAs), IFNα and IL-12. The combination of TAs with both cytokines yielded the most potent therapeutic response, resulting in the eradication of established liver metastases in several mouse models of the disease. Mechanistically, armed macrophages expanded tumor reactive CD8+ T cells, which in the presence of IFNα and IL-12 acquired features of progenitor exhausted T cells and killed cancer cells independently of CD4+ T cell help. IFNα and IL-12 produced within the liver tissue by armed macrophages rewired cell interactions within the tumor microenvironment and reprogrammed antigen presenting cells to further support T cell effector functions. Tumor reactive T cell rejuvenation and strong therapeutic activity were observed in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring private neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages expressing TA and immune-activating cytokines to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
2025-03-10 | GSE273608 | GEO
Project description:Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. This is partly attributable to the immunosuppressive microenvironment of liver metastases, which inhibits immune activation. To unleash anti-tumoral immune responses against liver metastases, we armed liver and tumor-associated macrophages to coordinately express tumor antigens (TAs), IFNα and IL-12. The combination of TAs with both cytokines yielded the most potent therapeutic response, resulting in the eradication of established liver metastases in several mouse models of the disease. Mechanistically, armed macrophages expanded tumor reactive CD8+ T cells, which in the presence of IFNα and IL-12 acquired features of progenitor exhausted T cells and killed cancer cells independently of CD4+ T cell help. IFNα and IL-12 produced within the liver tissue by armed macrophages rewired cell interactions within the tumor microenvironment and reprogrammed antigen presenting cells to further support T cell effector functions. Tumor reactive T cell rejuvenation and strong therapeutic activity were observed in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring private neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages expressing TA and immune-activating cytokines to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
2025-03-10 | GSE273606 | GEO
Project description:Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. This is partly attributable to the immunosuppressive microenvironment of liver metastases, which inhibits immune activation. To unleash anti-tumoral immune responses against liver metastases, we armed liver and tumor-associated macrophages to coordinately express tumor antigens (TAs), IFNα and IL-12. The combination of TAs with both cytokines yielded the most potent therapeutic response, resulting in the eradication of established liver metastases in several mouse models of the disease. Mechanistically, armed macrophages expanded tumor reactive CD8+ T cells, which in the presence of IFNα and IL-12 acquired features of progenitor exhausted T cells and killed cancer cells independently of CD4+ T cell help. IFNα and IL-12 produced within the liver tissue by armed macrophages rewired cell interactions within the tumor microenvironment and reprogrammed antigen presenting cells to further support T cell effector functions. Tumor reactive T cell rejuvenation and strong therapeutic activity were observed in distinct liver metastasis mouse models of colorectal cancer and melanoma, expressing either surrogate tumor antigens, naturally occurring private neoantigens or tumor-associated antigens. Altogether, our findings support the translational potential of in vivo armed liver macrophages expressing TA and immune-activating cytokines to expand and rejuvenate tumor reactive T cells for the treatment of liver metastases.
2025-03-10 | GSE273613 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15350: Resistance of primary ovarian cancer cells to oncolytic adenoviruses part1 of 2 GSE15351: Resistance of primary ovarian cancer cells to oncolytic adenoviruses part2 of 2 Refer to individual Series
2009-04-01 | E-GEOD-15473 | biostudies-arrayexpress
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 | PXD008023 | Pride
Project description:IntroductionImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).MethodsRecombinant Syrian hamster PD-L1 was expressed and mice immunized for mAb formation using hybridoma technology. Clonal selection through binding and functional studies in vitro, in silico and in vivo identified anti-PD-L1 clone 11B12-1 as the primary mAb candidate for immunotherapy modelling. The oncolytic virus (OV) and ICI combination approach was then evaluated using 11B12-1 and TILT-123 in a Syrian hamster model of pancreatic ductal adenocarcinoma (PDAC).ResultsSupernatants from hybridoma parent subclone 11B12B4 provided the highest positive PD-L1 signal, on Syrian hamster PBMCs and three cancer cell lines (HT100, HapT1 and HCPC1). In vitro co-cultures revealed superior immune modulated profiles of cell line matched HT100 tumour infiltrating lymphocytes when using subclones of 7G2, 11B12 and 12F1. Epitope binning and epitope prediction using AlphaFold2 and ColabFold revealed two distinct functional epitopes for clone 11B12-1 and 12F1-1. Treatment of Syrian hamsters bearing HapT1 tumours, with 11B12-1 induced significantly better (p<0.05) tumour growth control than isotype control by day 12. 12F1-1 did not induce significant tumour growth control. The combination of 11B12-1 with oncolytic adenovirus TILT-123 improved tumour growth control further, when compared to monotherapy (p<0.05) by day 26.ConclusionsNovel Syrian hamster anti-PD-L1 clone 11B12-1 induces tumour growth control in a hamster model of PDAC. Combining 11B12-1 with oncolytic adenovirus TILT-123 improves tumour growth control further and demonstrates good safety and toxicity profiles.
| S-EPMC9936529 | biostudies-literature