Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Co-transplantation of CAR-gene Engineered Precursor T Cells Leads To Suppressed T Cell Development and Increased NK Cell-based CAR-mediated Anti-leukemic Activity

ABSTRACT: Co-transplantation of CAR-gene Engineered Precursor T Cells Leads To Suppressed T Cell Development and Increased NK Cell-based CAR-mediated Anti-leukemic Activity

PROVIDER: PRJNA412882 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Co-transplantation of CAR-gene Engineered Precursor T Cells Leads To Suppressed T Cell Development and Increased NK Cell-based CAR-mediated Anti-leukemic Activity

Project description:CAR gene expression on precursor T cells (preTs) that have been generated in vitro from engineered hematopoietic stem cells may reduce the risk of leukemia relapse upon co-transplantation in an MHC-independent manner. Setting the expression of an anti-murine CD19 CAR under the control of an inducible promoter allowed time-dependent assessment of its impact on in vivo development. Adoptive transfer of engineered preTs along with T cell-depleted bone marrow resulted in potent anti-leukemia effects even in fully MHC-class I and II mismatched recipients. Anti-leukemia effects entirely relied on the in vivo development of CAR-expressing natural killer cells since NK cell depletion after transplantation resulted in a complete abrogation of anti-leukemic efficacy. Gene expression profiling revealed that enforced CAR expression on preTs led to an activated shift of transcriptional key factors to those being associated with NK cell development such as Nfil3, Id2, and Eomes. In contrast, CAR expression on preTs blocked thymic seeding completely and prevented further T cell development. The CAR-expressing NK cell progeny of transferred preTs persisted for up to 60 days post transplantation allowing for complete B-cell recovery thereafter. Taken together, we provide new functional insights for the use of CAR-engineered preTs allowing for potent anti-leukemia efficiency within a limited time window for on target/off tumor effects.

2017-10-03 | GSE104512 | GEO

Multi-Omic Single-Cell Dissection of Leukemic T-Cell Lymphoma Following CAR T-Cell Therapy

Project description:A 63-year-old male who received ciltacabtagene autoleucel (cilta-cel) CAR-T cells and the GPRC5DxCD3 bispecific talquetamab for early relapse of his multiple myeloma (MM) developed a leukemic peripheral T-cell lymphoma (PTCL) with cutaneous and intestinal involvement. Longitudinal single-cell RNA and T-cell receptor sequencing of peripheral blood and bone marrow revealed two hyperexpanded CAR-carrying, exhausted effector-memory T-cell clones with marked immunophenotypic as well as transcriptional alterations and different susceptibilities towards treatment with dexamethasone. Spatial transcriptomes of skin lesions confirmed the aberrant CAR-expressing T cells. Whole genome sequencing revealed three distinct integration sites, within the introns of ZGPAT, KPNA4, and polycomb-associated non-coding RNAs. Pre/post-CAR-T whole-genome analyses implicated clonal outgrowth of a TET2-mutated precursor propelled by additional sub-clone specific LOH and other secondary mechanisms

2025-01-05 | GSE283144 | GEO

Multi-Omic Single-Cell Dissection of Leukemic T-Cell Lymphoma Following CAR T-Cell Therapy [Spatial Transcriptomics]

2025-01-05 | GSE283145 | GEO

Monocyte-derived IL-1 and IL-6 are differentially required for cytokine release syndrome and neurotoxicity by CAR-T cells.

Project description:Single-cell transcriptome profiling using a 3' droplet-based platform (Chromium,10x Genomics) of human CD45+ leukocytes isolated from leukemic HuSGM3 mice infused with CD19.28z CAR-T cells, two days after cytokine release syndrome (CRS) onset and 5 days later.

2018-05-24 | E-MTAB-6505 | biostudies-arrayexpress

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

Gene expression analysis of leukemic samples in C57BL6 mice

Project description:[original title] Gene expression analysis of leukemic samples derived from AF4-MLL- or AF4-MLL/MLL-AF4-transduced and transplanted hematopoietic stem/precursor cells in C57BL6 mice. We used microarrays to analyze the global gene expression in leukemic cells with three distinct immunophenotypes. We compared leukemic cells isolated from the bone marrow of diseased mice and compared these profiles with normal bone marrow.

2010-07-07 | E-GEOD-20519 | biostudies-arrayexpress

Gene expression analysis of leukemic samples in C57BL6 mice

2010-07-07 | GSE20519 | GEO

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

2024-03-07 | GSE253982 | GEO

Gene expression profiles of chimeric cytokine receptor-engineered CAR-T cells

Project description:The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is suboptimal in most of the cancer types , necessitating further improvement in their therapeutic actions. However, enhancing antitumor T cell response inevitably confers an increased risk of cytokine release syndrome associated with monocyte-derived IL-6 secretion. Thus, a novel approach to simultaneously enhance therapeutic efficacy and safety is warranted. In this study, we developed a chimeric cytokine receptor composed of the extracellular domains of GP130 and IL6RA linked to the transmembrane and cytoplasmic domain of IL-7R mutant that constitutively activate JAK-STAT pathway (G6/7R). CAR-T cells with G6/7R efficiently absorbed and degraded monocyte-derived IL-6 both in vitro and in vivo. The G6/7R-expressing CAR-T cells showed superior expansion and persistence in vivo, which resulted in durable antitumor response in multple tumor models. Our strategy can be widely applicable to CAR-T cell therapy to enhance its efficacy and safety, irrespective of the target antigen.

2024-03-24 | GSE216734 | GEO

Leukemic hematopoiesis

Project description:Leukemic hematopoiesis

| PRJNA881262 | ENA