Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms

ABSTRACT: CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms

PROVIDER: PRJNA988531 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25056163_1.fastq.gz	Fastqsanger.gz
	SRR25056163_2.fastq.gz	Fastqsanger.gz
	SRR25056164_1.fastq.gz	Fastqsanger.gz
	SRR25056164_2.fastq.gz	Fastqsanger.gz
	SRR25056165_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms

Project description:Compared to CAR.CD19 T cells, we found that CAR.CD19 NKTs showed superior control of tumor growth in the B16-OVA-hCD19 melanoma model without evident toxicity. To investigate whetehr CAR.CD19 NKTs could affect the TME in the tumor. We used the single RNA seq to test the TME cell populations in the B16-OVA-hCD19 model between CAR.CD19 NKTs and CAR.CD19 Ts.

2024-08-21 | GSE236066 | GEO

A multimodal assay identifies optimized binders for a bicistronic CAR against GPC2 OR CD276 to overcome heterogeneity in Neuroblastoma

Project description:Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and remains deadly in patients with high-risk disease. Single chimeric antigen receptor T-cell therapies (CAR-T) for solid tumor have shown poor efficacy in clinical trials due, in part, to T cell exhaustion and uneven expression of target antigens in tumors. Here, we attempted to target Glypican-2(GPC2) and CD276(B7-H3), both highly but heterogeneously expressed on NB cell surface, to overcome these challenges in single CAR T- therapies. First, to identify optimal binders for CAR T- cell targeting each antigen, we made individual CAR constructs using multiple binders against these antigens and utilized a multimodal approach including simultaneous protein and transcriptome measurement at single cell level to characterize each individual CAR T- cell in a pooled strategy. Combined with cell expansion and cytotoxicity assays, we identified the most effective CAR construct for each target.

2022-03-18 | GSE181437 | GEO

SortaseA cleavable CD1d and H2Kb

Project description:Identification of SortaseA cleavable MHC class I proteins (CD1d, H2Kb) for shotgun lipidomics

2022-07-08 | PXD034366 | Pride

TN/SCM pre-selection generates CAR T-cell products driving superior anti-tumor responses while curtailing severe CRS

Project description:Chimeric antigen receptor (CAR) T-cell expansion and persistence represent key factors to achieve complete responses and prevent relapses. These features are typical of early memory T cells, which can be highly enriched through optimized manufacturing protocols. Here, we investigated the efficacy and safety profiles of CAR T-cell products generated from pre-selected naive/stem memory T cells (TN/SCM), as compared to unselected T cells (TBULK). Notwithstanding their reduced effector signature in vitro, limiting CAR TN/SCM doses showed superior antitumor activity and the unique ability to counteract leukemia re-challenge in hematopoietic stem/precursor cell-humanized mice, featuring increased expansion rates and persistence, together with an ameliorated exhaustion and memory phenotype. Most relevantly, CAR TN/SCM proved to be intrinsically less prone to induce severe cytokine release syndrome, independently of the costimulatory endodomain employed. This safer profile was associated with milder T-cell activation, which translated in reduced monocyte activation and cytokine release. These data suggest that CAR TN/SCM are endowed with a wider therapeutic index compared to CAR TBULK.

2022-05-17 | GSE200661 | GEO

CAR T cells, CAR NK cells and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines

Project description:Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR expressing T cells, NK cells and macrophages against glioblastoma, the most aggressive primary brain tumor. In vitro we show that T cell cancer killing is CAR-dependent, whereas intrinsic cytotoxicity overrules CAR-dependence for NK cells and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.

2024-12-03 | GSE283049 | GEO

Multimodal single-cell profiling reveals the enhanced antitumor activity of FGFR4/CD276 BiCisCAR T cells in rhabdomyosarcoma

Project description:We have generated a clinical grade CAR T targeting FGFR4 with a CD8 hinge and transmembrane domain (HTM) and a 4-1BB co-stimulatory domain (CSD) that is currently being developed for a clinical trial at the NCI. This standard FGFR4-CAR demonstrated potency in low burden RMS disease but has a more modest effect for bulky disease in RMS orthotopic model. Thus, we developed optimized FGFR4-CARs by modification of HTM or CSD to improve its efficacy. However, these modified FGFR4-CARs, even FGFR4.28HTM.28z CAR were unable to eradicate solid tumors in an more aggressive RMS559 model. CAR T cells targeting another cell surface protein CD276, a direct target of the RMS core-regulatory transcription factor MYOD1 is potent and effective, also could not eradicate the tumor. Therefore, we engineered a bicistronic CAR (BiCisCAR) to target both FGFR4 and CD276, with CD28 and 4-1BB CSDs, respectively, which showed remarkable and rapid tumor eradication compared with either single CAR alone. Here, we utilized a multimodal approach including simultaneous protein and transcriptome measurement at single cell level to characterize each FGFR4 or CD276 CAR T-cell infiltrating in RMS orthotopic xenografts. This assay further determined the molecular basis of superior antitumor effect of FGFR4.28HTM.28z-CD276.8HTM.BBz BiCisCAR T cells compared with other CARs.

2024-05-23 | GSE228127 | GEO

Highly Active CAR T Cells that Bind to a Juxta-Membrane Region of Mesothelin and are Not Blocked by Shed Mesothelin

Project description:Identification of the major protease sites in MSLN and preparation of a monoclonal antibody, 15B6, that binds next to cell membrane at the protease sensitive region and inhibits MSLN shedding. Mab 15B6 makes very active CAR-T cells whose activity is not blocked by shed MSLN. The 15B6 CAR-T cells have greatly superior anti-tumor activity in mice than CAR-T cells targeting an epitope in shed MSLN.

2022-04-13 | PXD033137 | Pride

The Second Generation of CAR-iMACs with Enhanced Polarization, CAR-mediated Efferocytosis and Superior Potency against Solid Tumors

Project description:The Second Generation of CAR-iMACs with Enhanced Polarization, CAR-mediated Efferocytosis and Superior Potency against Solid Tumors

| PRJNA884115 | ENA

The Second Generation of CAR-iMACs with Enhanced Polarization, CAR-mediated Efferocytosis and Superior Potency against Solid Tumors

Project description:Chimeric antigen receptor (CAR)-T cell therapies have shown great success in treating hematologic malignancies. Nonetheless, their therapeutic effect on solid tumors remains to be improved. Recently, macrophages have attracted great attention, given their ability to infiltrate solid tumors, phagocytize tumor cells as well as their immunomodulatory capacities. The first generation of CD3ζ-based CAR-macrophages demonstrated that the CAR could stimulate macrophage phagocytosis in a tumor antigen-dependent way. Here, we genetically engineered induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) with TLR4 intracellular TIR domain-containing CARs against EGFRvIII and GPC3, which yielded markedly enhanced antitumor effect in two different solid tumor models including glioblastoma, and hepatocellular carcinoma in which complete remission was achieved with CAR-iMACs alone or in combination with CD47 antibody. Moreover, the tandem CD3ζ-TIR-CAR, or the “second-generation” design of TIR-based dual signaling CAR, endowed iMACs with both target engulfment/efferocytosis capacity against antigen-expressing solid tumor cells, and potency of antigen-dependent M1 state polarization and M2 state resistance in an NF-κB dependent manner. We also illustrated a surprising mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we established the next generation CAR-iMACs equipped with orthogonal phagocytosis and polarization capacity for better antitumor functions in treating solid tumors.

2023-09-29 | GSE214140 | GEO

A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism

Project description:Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.

2024-05-02 | GSE264206 | 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