Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

ABSTRACT: Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

PROVIDER: PRJNA1306204 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

Project description:Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

| PRJNA1306205 | ENA

Epigenetic sequencing of allogeneic HSC-derived CAR-engineered NKT cells

Project description:CAR-T cell therapy has achieved remarkable clinical outcomes, yet the autologous nature of FDA-approved CAR-T products present significant challenges in manufacturing, cost, and patient selection. Therefore, there is a growing demand for off-the-shelf cell therapy. Here we introduce an ex vivo feeder-free culture to differentiate gene-engineered HSCs into allogeneic NKT cells, as well as their CAR-armed and IL-15-enhanced derivatives (Allo15CAR-NKT cells). In order to study the epigenetic regulation of the generated cells, we performed DNA methylation sequencing on both IL-15-enhanced and non-IL-15-engineered AlloCAR-NKT cells. Conventional CAR-T cells were included as a control.

2024-03-07 | GSE239648 | GEO

Single cell TCR sequencing of allogeneic HSC-derived CAR-engineered NKT cells

2024-03-07 | GSE253982 | GEO

Single cell RNA sequencing monitoring the development of allogeneic HSC-derived CAR-engineered NKT cells

2024-03-07 | GSE241996 | GEO

Single cell RNA sequencing to study the in vivo behaviour of allogeneic HSC-derived CAR-engineered NKT cells

2024-03-07 | GSE241998 | GEO

Allogeneic HSPC-engineered CD33-targeting CAR-NKT cells synergize with hypomethylating agents for effective and safe treatment of myeloid malignancies

Project description:Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for targeting myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, autologous approaches pose significant challenges in manufacturing and patient selection, emphasizing the need for off-the-shelf cell products. In this study, we systematically characterized primary AML and MDS patient samples, identifying a unique therapeutic opportunity for CAR-engineered invariant natural killer T (CAR-NKT) cell therapy. Utilizing a clinically guided culture method, we generated allogeneic IL-15-enhanced CD33-targeting CAR-NKT (Allo15CAR33-NKT) cells through HSPC engineering and an ex vivo, feeder-free HSPC differentiation culture. These cells demonstrated potent antitumor efficacy against blast cells via multiple tumor-targeting mechanisms. In vivo, Allo15CAR33-NKT cells exhibited effective tumor homing, expansion, and persistence, characterized by high effector function and low exhaustion propensity. Furthermore, these cells synergized with hypomethylating agent (HMA) treatment, which upregulated CD1d and NK ligand expression on tumor cells, enhancing susceptibility to Allo15CAR33-NKT cell-mediated killing. Notably, Allo15CAR33-NKT cells displayed minimal off-tumor effects against hematopoietic precursors, and low risks of graft-versus-host disease and cytokine release syndrome, highlighting their substantial therapeutic potential for myeloid malignancies.

2025-01-01 | GSE270430 | GEO

Epigenetic sequencing of allogeneic HSC-derived CAR-engineered NKT cells

Project description:Epigenetic sequencing of allogeneic HSC-derived CAR-engineered NKT cells

| PRJNA1000485 | ENA

Generation of off-the-shelf CAR-NKT cells for cancer immunotherapy with genetically engineered HSCs and feeder-free differentiation culture

Project description:Current CAR-T cell therapy's clinical potential is hampered by its autologous nature that poses significant challenges in manufacturing, costs, and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture to differentiate gene-engineered HSCs into allogeneic NKT cells and their CAR-armed derivatives (AlloCAR-NKT cells). The AlloCAR-NKT cells are generated at high yield, purity, and robustness. These cells exhibit potent antitumor efficacy, showing effective tumor homing, clonal expansion, and persistence In vivo. Impressively, AlloCAR-NKT cells can alter the tumor microenvironment by selectively depleting immunosuppressive TAMs and MDSCs, and can antagonize tumor immune evasion by deploying CAR/TCR/NKR triple-targeting mechanisms. AlloCAR-NKT cells also demonstrate an appealing safety profile with low GvHD and CRS risks, and exhibit a stable “hypoimmunogenic” phenotype attributed to epigenetic and signaling regulations. The reported technology presents a scalable strategy for diverse allogeneic CAR-NKT cell products, with potential for clinical translation and commercialization against various cancers.

2023-10-16 | GSE245375 | GEO

Single cell TCR sequencing of allogeneic HSC-derived CAR-engineered NKT cells

Project description:Single cell TCR sequencing of allogeneic HSC-derived CAR-engineered NKT cells

| PRJNA1068051 | ENA

Targeting Triple-Negative Breast Cancer Using Allogeneic Stem Cell-Engineered Mesothelin-Specific CAR-NKT Cells with Potent Antitumor Activity

Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of ER, PR, and HER2 expression. Its aggressive behavior, high degree of tumor heterogeneity, and immunosuppressive tumor microenvironment (TME) are associated with poor clinical outcomes, rapid disease progression, and limited therapeutic options. Although chimeric antigen receptor (CAR)-engineered T cell therapy has shown certain promise, its applicability in TNBC is hindered by antigen escape, TME-mediated suppression, and the logistical constraints of autologous cell production. In this study, we employed hematopoietic stem and progenitor cell (HSPC) gene engineering and a feeder-free HSPC differentiation culture to generate allogeneic IL-15-enhanced, mesothelin-specific CAR-engineered invariant natural killer T (Allo15MCAR-NKT) cells. These cells demonstrated robust and multifaceted antitumor activity against TNBC, mediated by CAR- and NK receptor-dependent cytotoxicity, as well as selective targeting of CD1d+ TME immunosuppressive cells through their TCR. In both orthotopic and metastatic TNBC xenograft models, Allo15MCAR-NKT cells demonstrated potent antitumor activity, associated with robust effector and cytotoxic phenotypes, low exhaustion, and a favorable safety profile without inducing graft-versus-host disease. Together, these results support Allo15MCAR-NKT cells as a next-generation, off-the-shelf immunotherapy with strong therapeutic potential for TNBC, particularly in the context of metastasis, immune evasion, and treatment resistance.

2025-07-31 | GSE304213 | 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