Ontology highlight
ABSTRACT:
PROVIDER: PRJNA655511 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12396419_1.fastq.gz | Fastqsanger.gz | |||
| SRR12396419_2.fastq.gz | Fastqsanger.gz | |||
| SRR12396420_1.fastq.gz | Fastqsanger.gz | |||
| SRR12396420_2.fastq.gz | Fastqsanger.gz | |||
| SRR12396421_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Neoantigen discovery in pediatric brain tumors is hampered by their low mutational burden and scant tissue availability. We developed a low-input proteogenomic approach combining tumor DNA/RNA sequencing and mass spectrometry proteomics to identify tumor-restricted (neoantigen) peptides arising from multiple genomic aberrations to generate a highly target-specific, autologous, personalized T cell immunotherapy. Our data indicate that novel splice junctions are the primary source of neoantigens in medulloblastoma, a common pediatric brain tumor. Proteogenomically identified tumor-specific peptides are immunogenic and generate MHC II-based T cell responses. Moreover, polyclonal and polyfunctional T cells specific for tumor-specific peptides effectively eliminated tumor cells in vitro. Targeting novel tumor-specific antigens obviates the issue of central immune tolerance while potentially providing a safety margin favoring combination with other immune-activating therapies. These findings demonstrate the proteogenomic discovery of immunogenic tumor-specific peptides and lay the groundwork for personalized targeted T cell therapies for children with brain tumors.
2021-11-02 | PXD029082 | Pride
Project description:In recent years the clinical success of T cell-based immunotherapy approaches has revolutionized treatment of solid tumors and hematological malignancies. However, still some patients do not respond to available therapies at all, others for limited time only. A promising low side-effect approach is peptide-based immunotherapy, which relies on specific immune recognition of tumor-associated human leucocyte antigen (HLA)-presented peptides. In this study, we developed a workflow for the immunopeptidome-guided design of off-the shelf warehouses for personalized peptide vaccines using the example of chronic lymphocyte leukemia (CLL). The so defined warehouses could provide the basis for different T cell-based immunotherapy approaches such as TCR-engineered T cell transfer or multi-peptide vaccinations. The warehouse approach enables a fast and cost-effective way to provide a personalized T cell-based immunotherapeutic approach. The here defined peptide warehouse is already utilized for a personalized multi-peptide vaccine trial (iVAC-XS15-CLL01, NCT04688385).
2021-09-10 | PXD024871 | Pride
Project description:The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. We characterized the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy subjects. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts. Relative to TAA, neoantigen-specific T cells are of higher structural avidity and, consistently, are preferentially detected in tumors. Effective tumor infiltration in mice models is associated with high structural avidity and CXCR3 expression. Based on TCRs biophysicochemical properties, we derived and applied an in silico model predicting TCR structural avidity and validated the enrichment in high avidity T cells in patients’ tumors. These observations indicate a direct relationship between neoantigen recognition, T cell functionality and tumor infiltration. These results delineate a rational approach to identify potent T cells for personalized cancer immunotherapy.
2023-05-18 | GSE232446 | GEO
Project description:The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. We characterized the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy subjects. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts. Relative to TAA, neoantigen-specific T cells are of higher structural avidity and, consistently, are preferentially detected in tumors. Effective tumor infiltration in mice models is associated with high structural avidity and CXCR3 expression. Based on TCRs biophysicochemical properties, we derived and applied an in silico model predicting TCR structural avidity and validated the enrichment in high avidity T cells in patients’ tumors. These observations indicate a direct relationship between neoantigen recognition, T cell functionality and tumor infiltration. These results delineate a rational approach to identify potent T cells for personalized cancer immunotherapy.
2023-05-18 | GSE232444 | GEO
Project description:Personalized cancer immunotherapy targeting patient-specific cancer/testis (CTA) antigens and neoantigens may benefit from large-scale tumor HLA peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. While significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumor provide a proxy for expansion of the patient tumor by re-grafting them through several passages to immune compromised mice. The HLA peptidomes of human biopsies were compared to those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared to the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. A large number of CTA-derived HLA peptides were discovered, as well as several neoantigens. Taken together, use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification potentially useful for personalized immunotherapy.
2020-05-27 | PXD016060 | Pride
Project description:Immunotherapy has shown great therapeutic potential for cancers with high tumor mutational burden (TMB), but much less promise for cancers with low TMB. One primary approach for adoptive lymphocyte transfer-based immunotherapy is to target the somatic mutated peptide neoantigens and cancer testis (CT) antigens recognized by cytotoxic T cells. Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ- associated peptides in both melanoma, a “hot tumor”, and EGFR mutant lung adenocarcinoma, a “cold tumor”. We uncovered 19 common driver oncogene-derived peptides and more than 1000 post-translationally modified peptides (PTM) representing 58 different PTMs. We constructed a CT antigen database with 286 antigens by compiling reputed CT antigen resources and “in-house” genomic data and used this to identify 45 CT antigen-derived peptides from the identified HLA peptidome. Using integrated next generation sequencing data, we discovered 12 neopeptides in EGFR mutant lung cancer cell lines. Finally, we report a novel approach for non-canonical peptide discovery, whereby we leveraged a deep learning-based de novo search and a high confidence annotated long noncoding RNA (LncRNA) database to identify 44 lncRNA-derived peptides. Findings of this study, for the first time, provide evidence for a large pool of actionable cancer antigen-derived peptides for use in mutant EGFR lung cancer immunotherapy.
2021-12-07 | PXD019774 | Pride
Project description:In the process of searching for tumor-specific mutations to predict neoantigens for cancer immunotherapy in a Lynch Syndrome mouse model, tumorigenesis was induced with 1% DSS in drinking water. DNA was isolated from tumors and colon tissue separately from 4 MLH1-KO mice using the DNeasy Qiagen kit according to the manufacturer's protocol. Purity of the DNA was confirmed to be very high with the NanoDrop before sending samples to Illumina for next generation sequencing with the Agilent SureSelect XT Mouse All Exon kit. Finally, an analysis was performed in which common tumor-specific mutations were processed through in silico antigen prediction software in NetMHC.
2021-10-02 | E-MTAB-10962 | biostudies-arrayexpress
Project description:Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial immunopeptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αβ sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor -T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial immunopeptides with potential to serve as immunotherapy targets in CRC.
2023-11-28 | PXD047311 |
Project description:The interaction of frameshift mutation-derived cancer neoantigens and cancer immunotherapy remains unknown. We found that live cell adjuvant or cDNA transfection in the muscle, which express MHC-class I and class II-restricted non-self-peptides, generated broad-spectrum anti-tumor immunity. Such chimeric peptides did not need to be tumor-neoantigens, but must be in a single chain (complete T cell antigen: CTA). Long product of frameshift mutation frequently contained CTA and the colon cancer patients with the long frameshift products (>120 amino acids) showed a good prognosis. Mechanistically, live cell adjuvant expressing CTA strengthened crosstalk between dendritic cells and CD8+ T cells in a CD4+ T cells-dependent manner. This cross talk suppressed CD8+ T cell exhaustion and produced stem-cell like progenitor CD8+ T cells in vivo. Combination of the live cell adjuvant conversed unresponsive tumors to responsive to PD-1 blockade therapy. Together, our findings provide a new broad-spectrum cancer immunotherapy, and clarify the type of frameshift neoantigens controlling the efficacy.
2024-10-16 | GSE245743 | GEO
Project description:Glioblastoma (GBM) patient outcomes remain low despite surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines, although most trials have used single tumor region sequencing to identify targetable antigens. This approach limits the antigen pool due to the heterogeneity of GBM tumors. We have implemented multisector sequencing to identify targetable neoantigens across the GBM tumor landscape that were then incorporated into personalized peptide vaccines called NeoVax. Here, we report the findings of four subjects enrolled on the trial. Following NeoVax, we observed a clonal expansion of CD8+ T cells in the peripheral blood that, when expanded in vitro, were reactive to, on average, half of the NeoVax neoantigens tested by IFN-g ELISPOT, including BRAF V600E in one subject. A post-NeoVax tumor biopsy was resected from one subject and also showed evidence of infiltrating CD8+ T cell clonal expansion. Although the patients enrolled in this trial did not achieve remission, this pilot study demonstrates the feasibility of NeoVax and the importance of multisector sampling for neoantigen screening.
2024-04-12 | GSE237936 | GEO