Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening

ABSTRACT: Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening

PROVIDER: PRJNA803463 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR17884300_1.fastq.gz	Fastqsanger.gz
	SRR17884300_2.fastq.gz	Fastqsanger.gz
	SRR17884301_1.fastq.gz	Fastqsanger.gz
	SRR17884301_2.fastq.gz	Fastqsanger.gz
	SRR17884302_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 72

Similar Datasets

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [scRNA-seq]

Project description:Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [scRNA-seq]

| PRJNA803465 | ENA

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [scRNA-seq]

Project description:CAR-T cells are a promising new treatment for B cell malignancies. However, the majority of patients inevitably go on to experience disease relapse through largely unknown means. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screening in an immunocompetent murine model of B cell acute lymphoblastic leukemia (B-ALL). We identified IFN /JAK/STAT signaling and components of the antigen processing and presentation pathway as key mediators of resistance to anti-CD19 CAR-T therapy in vivo, but not in vitro. Transcriptional characterization of this model demonstrated an upregulation of these pathways in CAR-T treated relapsed tumors, and examination of data from CAR-T treated B-ALL patients revealed an association between poor outcomes and increased expression of JAK/STAT/MHC-I in leukemia cells. Together, our data identify an unexpected mechanism of resistance to immunotherapy, in which tumor cell interaction with IFN -secreting CAR-T cells in vivo activates the expression of an MHC-I inhibitory T cell program.

2023-10-31 | GSE196142 | GEO

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [bulk RNA-seq]

2023-10-31 | GSE196135 | GEO

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [bulk RNA-seq]

Project description:Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening [bulk RNA-seq]

| PRJNA803457 | ENA

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies [GSC]

Project description:Glioblastoma (GBM) is the most prevalent primary malignant brain tumor, containing self-renewing stem-like GBM stem cells (GSCs) that have been a focus of immunotherapies. Chimeric antigen receptor (CAR) T cell therapy has shown evidence of clinical activity, but overall limited responses in patients with GBMs. Here, we interrogated molecular determinants of CAR T cell-mediated GBM killing through whole-genome CRISPR screens in both CAR T cells and patient-derived GSCs. CRISPR screening of CAR T cells identified dependencies for their effector functions, including TLE4 and IKZF2. Targeted knockout of these genes in CAR T cells robustly enhanced antitumor efficacy against GBM patient-derived xenografts (PDXs). Bulk and single cell-RNA sequencing of edited CAR T cells revealed transcriptional profiles of superior effector function and inhibited exhaustion responses. Reciprocal screening of GSCs identified genes essential for their susceptibility to CAR-mediated killing, including RELA and NPLOC4, the knockout of which altered the tumor-immune signaling axis and increased responsiveness of CAR therapy. Overall, CRISPR screening of CAR T cells and GSCs are promising strategies to discover avenues and inform potential combinatorial approaches for enhancing CAR T cell therapeutic efficacy against GBM, and can be extended to reveal key mediators of immunotherapy responses across solid tumors.

2021-05-19 | GSE163401 | GEO

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies [bulk]

2021-05-19 | GSE163400 | GEO

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies [single-cell]

2021-05-19 | GSE163715 | GEO

Leukemia-intrinsic determinants of CAR-T response revealed by in vivo genome-wide CRISPR screening

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-30 | GSE196143 | GEO

Pooled screening for CAR function in glioblastoma

Project description:Pooled screening for CAR function in glioblastoma

| PRJNA1081276 | ENA

Pooled screening for CAR function in glioblastoma

Project description:Human primary CD3+ T cells expressing IL13Ra2-targeted chimeric antigen receptors (CARs) that had been identified through high throughput pooled screening were rechallenged with an IL13Ra2+ human glioblastoma cell line , then stained with CITESEQ antibodies indicative of T cell memory and exhaustion state and prepared for single cell sequencing in order to determine their phenotypic responses to chronic tumor challenge relative to that of a clinical standard CAR.

2024-04-19 | GSE259352 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data