Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA932953 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CAR T cells targeting uPAR are effective senolytics
| PRJNA607785 | ENA
Project description:Chimeric antigen receptor (CAR)-modified T-cells have become established as an effective treatment of haematological cancers. In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukaemia (B ALL), CD19 targeting CAR T-cells often induce durable remissions. Previously, we generated a novel low-affinity CAR incorporating a CD19-specific single-chain variable fragment (scFV) called CAT, displaying a faster off-rate of interaction than the FMC63 CD19 binder used in prior clinical studies. Here, we systematically analysed CD19 CAR T-cells of ten children with relapsed or refractory B ALL enrolled in the CARPALL trial (NCT02443831). To characterize persisting CD19 CAR T-cells, we performed high throughput single-cell gene expression and T-cell receptor (TCR) sequencing of infusion products and serial blood and bone marrow samples up to five years post-infusion. We isolated CAR T-cells from peripheral blood or bone marrow by flow cytometry for CD3 and CAR expression, prior to single cell sequencing (Chromium 10X) platform.
| EGAD00001010018 | EGA
Project description:Point mutations within the TERT promoter are the most common recurrent somatic non-coding mutation identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma and bladder cancer. They are most abundant at C146T and C124T and more rare at A57C, with the latter originally described as a familial case but subsequently shown also to occur somatically. All three mutations create de novo ETS (E-twenty-six specific) binding sites and result in the reactivation of the TERT gene, allowing cancer cells to achieve replicative immortality. Here, we employed a systematic proteomics screen to identify transcription factors preferentially binding to the C146T, C124T and A57C mutations. While we confirmed binding of multiple ETS factors to the mutant C146T and C124T sequences, we identified E4F1 a an A57C-specific binder and ZNF148 as a TERT WT binder that is excluded from the TERT promoter by the C124T allele. Both proteins are activating transcription factors that bind specifically to the A57C and wildtype (at position 124) TERT promoter sequence in corresponding cell lines and upregulate TERT transcription and telomerase activity.
2023-11-04 | PXD037776 | Pride
Project description:De novo peptide sequencing is a fundamental research area in mass spectrometry (MS) based proteomics. However, those methods have often been evaluated using a couple of simple metrics that do not fully reflect their overall performance. Moreover, there has not been an established method to estimate the false discovery rate (FDR) and the significance of de novo peptide-spectrum matches (PSMs). Here we propose NovoBoard, a comprehensive framework to evaluate the performance of de novo peptide sequencing methods. The framework consists of diverse benchmark datasets (including tryptic, nontryptic, immunopeptidomics, and different species), and a standard set of accuracy metrics to evaluate the fragment ions, amino acids, and peptides of the de novo results. More importantly, a new approach is designed to evaluate de novo peptide sequencing methods on target-decoy spectra and to estimate their FDRs. Our results thoroughly reveal the strengths and weaknesses of different de novo peptide sequencing methods, and how their performances depend on specific applications and the types of data. Our FDR estimation also shows that some tools may perform better than the others in distinguishing between de novo PSMs and random matches, and can be used to assess the significance of de novo PSMs.
2024-08-28 | PXD055277 | Pride
Project description:CAR-T cells have been used to treat patients with glioblastoma (GBM) in clinical trial settings, by targeting GBM-associated antigens. However, the efficacy of these CAR-T cells remain limited mainly due to heterogeneous expression of tumor antigen and their anergy in tumor microenvironment (TME). Cytokine-inducible SH2-containing protein (CIS, encoded by the gene CISH) is a potent intracellular checkpoint inducing T cell anergy. Here, we identified fibroblast activation protein alpha (FAPα) as a highly attractive target for CAR-T cell therapy against GBM based on its dual expression pattern (on tumor cells and perivascular cells) in GBM. A panel of nanobodies specific for FAPα were then isolated using a yeast surface display library. FAPα-targeting CAR-T cells were developed using the isolated nanobody and verified for their specific cytotoxicity to GBM cells. Furthermore, a non-viral circular single-stranded DNA (cssDNA)-based CRISPR/Cas9 targeted genome editing (cssDNA/CRISPR/Cas9) technology was used to integrate CAR cassettes at CISH locus to generate CISH-knockout (CISH-KO) CAR-T cells. The resulted CISH-KO CAR-T cells exhibited robust proliferation and potent anti-GBM activity in vitro and in vivo compared with conventional lentivirus-transduced CAR-T cells. Our proof-of-concept study demonstrates that CISH-KO FAPα-targeting CAR-T cells engineered by non-viral locus-specific integration represent a promising therapeutic approach for GBM.
2025-12-25 | GSE314496 | GEO
Project description:We explore whether introducing two chimeric antigen receptor (CAR) molecules with distinct signaling motifs into a single T cell improves CAR T cell (CART) efficacy against leukemia and lymphoma. RNA expression profiling demonstrated that T cells co-expressing two CARs that recognize the same target in which one CAR was linked to CD28 costimulation and the other was linked to 4-1BB costimulation augmented canonical NF-κB, non-canonical NF-κB, and Th17 differentiation pathways equivalently upon target engagement. Interestingly, multitargeted CARTs transcriptional profile favored the costimulatory domain linked to the binder of the more robustly expressed CD19 rather than one linked to the binder of the less expressed CD22 upon tumor engagement. In vivo and T cell exhaustion assays found that multitargeted T cells with distinct signaling domains led to greater durable control of B-ALL than single targeted Dual CAR T cells with T cells co-expressing CD19.BBζ and CD22.28ζ being the most potent. Together, this data indicates that optimal pairing of CAR binder domain with signaling cassette bolsters anti-tumor efficacy by improving both T cell durability and effector function.
2025-08-13 | GSE296016 | GEO