Similar Datasets
Project description:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. Intratumoral administration is conceivably safer than systemic delivery and allows concentrate proinflammatory adjuvanticity in the tumor microenvironment and tumor-draining lymphoid tissue. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and that upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment of subcutaneous tumors derived from MC38, 4T1 and B16F10 with BO-112 leads to remarkable local disease control mediated by CD8+ T lymphocytes, as concluded from selective depletion experiments. Some degree of control of non-injected tumor lesions upon BO-112 intratumoral treatment was found in mice bearing bilateral B16OVA melanomas, that was enhanced when co-treated with systemic anti-CD137 and anti-PD-L1 immunomodulatory mAbs. More abundant CD8+ T lymphocytes were found in tumor-draining lymph nodes and in the tumor microenvironment following intratumoral treatment with BO-112. Enhanced numbers of tumor-specific CTLs recognizing melanosomal antigens and ovalbumin were readily detected among them. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098) and our results in mice suggest prominent anti-tumor local control through its proimmune effects. To compare the in-vitro and in vivo transcriptional profile induced by BO-112, B16-OVA cell lines were incubated with BO-112 for 24h. BO-112 induces a specific transcriptional profile in B16-OVA cell cultures. Key immunoregulatory genes were found to be differentially expressed between BO-112 and Vehicle-incubated B16-OVA cells.
2019-05-15 | GSE116075 | GEO
Project description:Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. Intratumoral administration is conceivably safer than systemic delivery and allows concentrate proinflammatory adjuvanticity in the tumor microenvironment and tumor-draining lymphoid tissue. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and that upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment of subcutaneous tumors derived from MC38, 4T1 and B16F10 with BO-112 leads to remarkable local disease control mediated by CD8+ T lymphocytes, as concluded from selective depletion experiments. Some degree of control of non-injected tumor lesions upon BO-112 intratumoral treatment was found in mice bearing bilateral B16OVA melanomas, that was enhanced when co-treated with systemic anti-CD137 and anti-PD-L1 immunomodulatory mAbs. More abundant CD8+ T lymphocytes were found in tumor-draining lymph nodes and in the tumor microenvironment following intratumoral treatment with BO-112. Enhanced numbers of tumor-specific CTLs recognizing melanosomal antigens and ovalbumin were readily detected among them. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098) and our results in mice suggest prominent anti-tumor local control through its proimmune effects. Intratumoral administration of BO-112, a nanoplexed form of PolyI:C, triggers an efficacious antitumor response in different tumor models as a consequence of proimmflamatory activity and its direct effects in tumor cells. BO-112 local administration induces direct tumor cell death by apoptosis, showing signs of immunogenic cell death, and a strong release of IFNα/β and other proinflammatory mediators. As a result, a tumor-specific CD8+ immune response is mounted or augmented to the point of controlling tumor progression both in the locally injected lesion and to some extent on distantly implanted tumor nodules
2019-05-15 | GSE116074 | GEO
Project description:This is an open, single arm, multicenter phase 2 trial in which BO-112 will be administered intratumorally in combination with intravenous pembrolizumab in patients with liver metastasis from colorectal, gastric or gastroesophageal junction cancers. The objective is to reverse the primary resistance that a subgroup of patients from these tumors having microsatellite stability present to the PD-1 inhibitors. Treatment will be administered every 3 weeks, with the exception of the first cycle, in which BO-112 will be also administered on D8, for up to 2 years.
The primary objective is overall response rate based on RECIST 1.1 and safety, specifically referred to treatment emergent adverse events (TEAEs) with severity ≥ Grade 3 related to the study treatment (NCI-CTCAE v 5.0). The secondary endpoints include other efficacy endpoints (duration of response, disease control rate, progression-free survival, overall survival at 6 months, all based on RECIST 1.1, and overall response rate based on a specific tumor assessment criteria to evaluate the response to immunotherapies, IRECIST) and safety, in this case considering the number and proportion of subjects with treatment TEAEs (any grade) . In addition, the changes in the tumor microenvironment induced by the injection of BO-112 will be also evaluated as exploratory endpoints.
| 2348431 | ecrin-mdr-crc
Project description:Here we analyzed through single cell RNA sequencing multiple samples derived from patients with three different types of soft tissue sarcoma, including liposarcoma, undifferentiated pleomorphic sarcoma, and myxofibrosarcoma, participating in a clinical trial that evaluates the efficacy of intra-tumoral BO-112 injection with or without Nivolumab and pre-operative radiation therapy. The goal of this study is to analyze the changes in the tumor-microenvironment associated with the treatments administered.
2025-07-15 | GSE279852 | GEO
Project description:Bulk RNAseq of pancreatic stellate cells (PSC) treated with DMXAA, interferon gamma or DMSO control. PSC were cultured alone as mono-cultures or in co-culture with mouse tumour organoids, The PSC were recovered by FACS using fluorecent protein mKate-2.
2025-03-19 | E-MTAB-14943 | biostudies-arrayexpress
Project description:Bulk RNAseq of pancreatic stellate cells (PSC) and tumour cells treated with STING agonist DMXAA, STING inhibitor H151 or DMSO control. PSC were cultured alone as mono-cultures or in co-culture with mouse tumour organoids, The PSC and tumour cells were recovered by FACS using fluorecent proteins mKate-2 and tGFP, respectively.
2025-03-19 | E-MTAB-14946 | biostudies-arrayexpress
Project description:Brain organoids (BO) enabled the investigation of human corticogenesis in-vitro with an increasing range of protocols achieving its remarkable recapitulation. However, we lack a resource gathering fetal cortex-specific gene co-expression patterns and their behavior in BO. We complement the current knowledge with a benchmarking of BO versus human corticogenesis, integrating: transcriptomes from in-house differentiated cortical BO (CBO), in-house processed human fetal brain samples, analysis of transcriptomes from different BO systems and of pre-natal cortical samples from the BrainSpan Atlas.
2022-12-31 | E-MTAB-11239 | biostudies-arrayexpress
Project description:This dataset contains RNAseq experiments of in vitro cultured MC38 colon cancer cell line treated with PBS or 5-FU
2021-01-01 | GSE160985 | GEO
Project description:We designed a novel intratumoral (IT) IL-12 mRNA therapy to promote local IL-12 tumor production whilst mitigating systemic effects. A single IT dose of mouse (m)IL-12 mRNA induced IFNγ and CD8+ T cell-dependent tumor regression in multiple syngeneic mouse models including MC38-R, and animals with a complete response demonstrated immunity to re-challenge. In order to further investigate the impact of mIL-12 mRNA on the MC38-R TME, we performed tumor transcriptomic evaluation 24h and 7 days after a single IT dose of 0.5 micrograms IL-12 or control mRNA. mRNA was isolated from snap-frozen syngeneic tumors using an RNeasy mini kit (Qiagen) and quantified on the Affymetrix mouse 430 2.0 microarray.
2020-09-01 | E-MTAB-9316 | biostudies-arrayexpress