Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impact of CD4+ T cell help on CD8+ CAR T cell gene expression during ex-vivo manufacturing

ABSTRACT: Cell culture conditions impact the clinical efficacy of chimeric antigen receptor (CAR) T cell products, but the optimal approach remains unknown. Separate CD4+ and CD8+ cultures offer a potential advantage but complicate manufacturing and may affect cell expansion and function. We evaluated the co-culture of CD4+ and CD8+ cells at a defined ratio at culture initiation. We observed that the presence of CD4+ cells markedly improves expansion of CD8+ CAR T cells, and CD8+ cells cultured in isolation exhibit a hypofunctional phenotype and transcriptional signature compared with those co-cultured with CD4+ cells. Mixed-culture CAR T cells also confer superior anti-tumor activity in vivo compared with separately expanded, co-infused cells. CD4+ cell effects on CD8+ cells are mediated through both cytokines and direct cell contact, including CD40L-CD40 and CD70-CD27 interactions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245427 | GEO | 2023/11/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

E-MTAB-5338

Project description:RNAseq analysis of CD4 and CD8 T cells in response to vaccinia virus infection

2019-05-14 | E-MTAB-5338 | ExpressionAtlas

E-GEOD-6740

Project description:Transcription profiling by array of human CD4+ and CD8+ T cells from HUV patients

2025-01-24 | E-GEOD-6740 | ExpressionAtlas

NOTCH1 signaling during CD4+ T-cell activation alters transcription factor networks and enhances antigen responsiveness [CULTURED_NCT07]

Project description:Adoptive transfer of T cells expressing chimeric antigen receptors (CAR-T) effectively treats refractory hematologic malignancies in a subset of patients but can be limited by poor T-cell expansion and persistence in vivo. Less differentiated T-cell states correlate with the capacity of CAR-T to proliferate and mediate antitumor responses, and interventions that limit tumor-specific T-cell differentiation during ex vivo manufacturing enhance efficacy. NOTCH signaling is involved in fate decisions across diverse cell lineages and in memory CD8+ T cells was reported to upregulate the transcription factor FOXM1, attenuate differentiation, and enhance proliferation and antitumor efficacy in vivo. Here, we used a cell-free culture system to provide an agonistic NOTCH1 signal during naïve CD4+ T-cell activation and CAR-T production and studied the effects on differentiation, transcription factor expression, cytokine production, and responses to tumor. NOTCH1 agonism efficiently induced a stem cell memory phenotype in CAR-T derived from naïve but not memory CD4+ T cells and upregulated expression of AhR and c-MAF, driving heightened production of interleukin-22 (IL-22), IL-10, and granzyme B. NOTCH1-agonized CD4+ CAR-T demonstrated enhanced antigen responsiveness and proliferated to strikingly higher frequencies in mice bearing human lymphoma xenografts. NOTCH1-agonized CD4+ CAR-T also provided superior help to cotransferred CD8+ CAR-T, driving improved expansion and curative antitumor responses in vivo at low CAR-T doses. Our data expand the mechanisms by which NOTCH can shape CD4+ T-cell behavior and demonstrate that activating NOTCH1 signaling during genetic modification ex vivo is a potential strategy for enhancing the function of T cells engineered with tumor-targeting receptors.

2022-07-03 | GSE207314 | GEO

NOTCH1 signaling during CD4+ T-cell activation alters transcription factor networks and enhances antigen responsiveness [IN_VIVO_AW3]

2022-07-03 | GSE207312 | GEO

E-MTAB-6849

Project description:RNAseq of human bone marrow mesenchymal stem cells in co-culture with endothelial cells

2025-01-23 | E-MTAB-6849 | ExpressionAtlas

E-GEOD-40613

Project description:Effects of co-culture of Endothelial Cells with Mesenchymal Stem Cells on Gene Expression

2025-01-24 | E-GEOD-40613 | ExpressionAtlas

E-GEOD-14926

Project description:Transcription profiling by array of human CD4 positive and CD8 positive T cells selected by positive or negative immunomagnetic cell selection

2025-01-24 | E-GEOD-14926 | ExpressionAtlas

Clonal kinetics and single cell transcriptional profiling of adoptively transferred CD19-specific CD8+ CAR-T cells in adults with B cell malignancies

Project description:Lymphodepletion chemotherapy followed by infusion of T cells modified to express a CD19-targeting chimeric antigen receptor (CAR) has produced remarkable anti-tumor responses in patients with B cell malignancies. However, little is known about the clonal composition and transcriptional heterogeneity of CAR-T cells in the infusion products (IP) and clonal kinetics after adoptive transfer. We performed single-cell RNA sequencing (scRNA-seq) on CD8+ CAR-T cells isolated from the IP and the blood of patients treated on a phase 1 clinical trial (NCT01865617) with lymphodepletion chemotherapy and a defined formulation of CD4+ and CD8+ CD19-specific CAR-T cells. Infused CD8+ CAR-T cells displayed transcriptional heterogeneity which declined after adoptive transfer, coincident with early expression of genes associated with activation. We identified four transcriptionally distinct CAR-T cell subsets in the IP and found that these subsets differed in their contributions to the CAR-T cell population detected in blood after infusion. Better understanding of the kinetics of clonal expansion of CAR-T cells after adoptive transfer may provide insight into strategies to improve CAR-T cell immunotherapy.

2019-11-22 | GSE125881 | GEO

The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state and its deletion improves checkpoint blockade

Project description:CD8+ T cell exhaustion (TEX) impairs the ability of T cells to clear chronic infection or cancer. While TEX are hypofunctional, some TEX retain effector gene signatures, a feature that is associated with expression of KLRs (killer lectin-like receptors). Although KLR+ TEX may improve control of chronic antigen, the signaling molecules regulating this population are poorly understood. Using scRNA-seq, flow cytometry, RNA velocity, and scTCR-seq, we demonstrated that deleting the pseudokinase Trib1 shifted TEX towards CX3CR1+ intermediates (TINT) with robust enrichment of KLR+ TEX (TKLR) via clonal T cell expansion. Adoptive transfer studies demonstrate this shift towards a CD8+ TKLR in Trib1 deficient cells is CD8-intrinsic, while CD4-depletion studies demonstrate that CD4+ T cells are required for optimal viral control in Trib1 conditional knockout mice. Further, Trib1 loss augmented anti-PD-L1 blockade to improve viral clearance. These data identify Trib1 as an important regulator of CD8+ TEX whose targeting enhances the TKLR effector state and improves checkpoint inhibitor therapy.

2023-07-25 | GSE235530 | GEO

Bulk mRNA Seq CAR.CCR7 vs. CAR

Project description:The study aimed to elucidate the transcriptional changes introduced by genetic engineering of CAR T cells to stably express the homeostatic chemokine receptor CCR7. In vitro killing assays hinted to a higher cytolytic capacity that could be tied to an altered cytoskeletal rearrangement. Human CAR and CAR.CCR7 T cells were generated by retroviral transduction and enriched by FACS at the end of the expansion phase (day 10), either without or with a previous over-night co-culture with target Jeko1 tumor cells that express the CAR target antigen CXCR5. Enriched cells were immediately processed for bulk mRNA Seq

2023-06-30 | E-MTAB-12778 | biostudies-arrayexpress

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