4e46bc06-f424-4013-aab0-d679fe395109 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001011074 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Thirty patients with advanced melanoma were recruited to a clinical trial investigating the therapeutic cancer vaccine, UV1, in combination with pembrolizumab. Whole exome sequencing was performed on melanoma biopsies to determine tumor mutational burden and association with response to therapy. RNA sequencing of matched tumor biopsies to evaluate gene expression profiles at baseline and post-treatment.
| EGAS00001007210 | EGA
Project description:Samples are from a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 given in combination with pembrolizumab, conducted in patients with advanced non-small cell lung cancer. Single cell RNA sequencing of pre- and post-transduced vaccines was performed to characterize the cellular composition of these vaccines and assess the trascriptional impact of the transduction process. The same vaccine production procedure was also applied to blood obtained from healthy donors to investigate the effects of donor source on DC vaccine phenotype.
2024-11-14 | GSE272174 | GEO
Project description:This is a simple mathematical population model for pembrolizumab-treated advanced melanoma patients, used to predict the response of melanoma patients to immune checkpoint inhibitors.
2024-09-02 | BIOMD0000000838 | BioModels
Project description:<p>Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier <a href='https://clinicaltrials.gov/study/NCT03772899' rel='noopener noreferrer' target='_blank'>NCT03772899</a> .</p>
2025-02-27 | MTBLS711 | MetaboLights
Project description:This study demonstrates two fundamental tenets of immunotherapy: vaccines targeting any tumor antigen will not be as effective as those targeting true oncogenic drivers and neither the stimulation of tumor-specific T-cells nor the blockade of a key immune checkpoint is enough to overcome the layers of immune suppression by itself. It provides single cell genetic evidence that vaccination alone generates a population of CD8 T-cells incapable of long-term tumor control due to the activation of numerous immune dysfunction pathways within the tumor. These promising studies have led to the initiation of a Phase II clinical trial testing a novel HER2 vaccine in combination with Pembrolizumab (NCT03632941) to determine if this combination can elicit effective anti-tumor immunity while minimizing off-target immune responses in patients with advanced HER2+ BC.
2020-04-11 | GSE148480 | GEO
Project description:This study demonstrates two fundamental tenets of immunotherapy: vaccines targeting any tumor antigen will not be as effective as those targeting true oncogenic drivers and neither the stimulation of tumor-specific T-cells nor the blockade of a key immune checkpoint is enough to overcome the layers of immune suppression by itself. It provides single cell genetic evidence that vaccination alone generates a population of CD8 T-cells incapable of long-term tumor control due to the activation of numerous immune dysfunction pathways within the tumor. These promising studies have led to the initiation of a Phase II clinical trial testing a novel HER2 vaccine in combination with Pembrolizumab (NCT03632941) to determine if this combination can elicit effective anti-tumor immunity while minimizing off-target immune responses in patients with advanced HER2+ BC.
2020-04-11 | GSE148478 | GEO
Project description:This study demonstrates two fundamental tenets of immunotherapy: vaccines targeting any tumor antigen will not be as effective as those targeting true oncogenic drivers and neither the stimulation of tumor-specific T-cells nor the blockade of a key immune checkpoint is enough to overcome the layers of immune suppression by itself. It provides single cell genetic evidence that vaccination alone generates a population of CD8 T-cells incapable of long-term tumor control due to the activation of numerous immune dysfunction pathways within the tumor. These promising studies have led to the initiation of a Phase II clinical trial testing a novel HER2 vaccine in combination with Pembrolizumab (NCT03632941) to determine if this combination can elicit effective anti-tumor immunity while minimizing off-target immune responses in patients with advanced HER2+ BC.
2020-04-11 | GSE148477 | GEO
Project description:Importance: Autophagy has been identified as a resistance mechanism to BRAF and MEK inhibition in BRAF mutant melanoma. In the BAMM trial, hydroxychloroquine (HCQ) was used to inhibit autophagy in combination with dabrafenib and trametenib in BRAF mutant melanoma patients. Objective: To a) determine safety and maximal tolerated dose (MTD) of hydroxychloroquine when combined with dabrafenib and trametinib and b) determine antitumor activity of the combination. Design: Open label non-randomized phase I/II clinical trial Setting: Prospective therapeutic clinical trial conducted in 4 centers Participants: Unresectable Stage III or Stage IV BRAF mutant melanoma patients Intrevention: HCQ twice daily, dabrafenib 150 mg twice daily and trametinib 2 mg daily (D+T) Main Outcome: Primary outcomes were safety and 1-year progression-free survival (PFS) rate Results: Between December 2014 and January 2020, 50 patients were screened, 38 patients were enrolled and evaluable for toxicity and 34 patients were evaluable for 1-year PFS rate. Patient demographics were: 29% were ECOG PS 1, 47% had elevated LDH, 52% were Stage IV M1c or M1d and 53% had previously received therapy for advanced melanoma. In the phase I trial there was no dose limiting toxicity of HCQ at either 400 (n=3) or 600 (MTD) mg po bid combined with D+T. For the entire study population, the 1-year PFS rate was 41% (95% CI = ), median PFS was 11.9 months (95% CI = ), overall response rate (ORR) was 85% (95% exact CI=64-95%)and complete response rate of 41% (95% exact CI=25-59%). In a prespecificed subgroup analysis in 18 patients with elevated LDH, the ORR was 88% and median PFS was 8 months Conlusion and Relevance: The combination of HCQ, dabrafenib and trametinib was well tolerated and produced a high response rate but did not meet the prespecified criteria for success with respect to the 1-year PFS rate. In patients with elevated LDH , the response rate and PFS were encouraging. A randomized placebo controlled trial of dabrafenib and trametinib with/without HCQ in advanced BRAF mutant melanoma patients with elevated LDH and previously treated with immunotherapy is being conducted through the National Clinical Trial Network.
2022-01-07 | GSE193157 | GEO
Project description:The metastatic form of Melanoma has a reported ten-year survival rate of approximately 15%. Clinical trials have shown modest success in a subset of patients. Particularly, combinational therapy using checkpoint blockade has shown the most success, but many patients do not respond. The patients that do respond to treatments often have a pre-existing antitumor immunity. To generate an optimal anti-tumor immune response, we have previously created a dendritic cell (DC) based adenovirus vaccine targeted against three common melanoma associated antigens: Tyrosinase, MART-1, and MAGE-A6 (TMM2). The vaccine was used in a Phase 1 clinical trial (NCT01622933) , where 35 patients were enrolled. Immature DC (iDC) were generated from patient monocytes (GM-CSF + IL-4), matured (mDC) using IFNG + LPS, and transduced with the adenovirus vaccine (AdVTMM2 DC). Patients received three intradermal injections of the vaccine over the course of one month. Human genome RNA microarray was used to analyze the gene expression profiles of the DC vaccine for each patient.
2020-09-10 | GSE157738 | GEO
Project description:Many cancer patients don’t benefit from currently-approved immune checkpoint inhibitors (ICI), suggesting that additional immunomodulation of the immunosuppressive tumour microenvironment (TME) is required. MTL-CEBPA specifically upregulates expression of master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report the safety, tolerability, pharmacokinetics, and efficacy of MTL-CEBPA in combination with pembrolizumab in patients with advanced solid tumours that typically show ICI resistance. Multimodal exploratory analyses of paired patient biopsies demonstrate biological changes associated with combination treatment of MTL-CEBPA and pembrolizumab, including increased infiltration of T cell and antigen-presenting cells supporting conversion from an immune desert towards a more immune-inflamed TME. Patients with disease stabilisation demonstrate reductions in immunosuppressive myeloid cells post-treatment. Collectively, these data support a role for MTL-CEBPA in reducing immunosuppression in the TME. This study was registered at ClinicalTrials.gov (NCT04105335). This manuscript also reports proteomic data from patients treated with MTL-CEBPA in combination with sorafenib from clinical trial, OUTREACH, accessible at ClinicalTrials.gov, number NCT02716012 and reported. Stored plasma from patients from this clinical trial were analysed using OLINK as described below.
2025-05-07 | PXD060726 | Pride