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A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [ATAC-Seq]

ABSTRACT: A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [ATAC-Seq]

PROVIDER: PRJNA1085330 | ENA |

REPOSITORIES: ENA

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A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells

Project description:A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells

| PRJNA1085332 | ENA

A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [RNA-Seq]

Project description:A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [RNA-Seq]

| PRJNA1085492 | ENA

A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [ATAC-Seq]

Project description:Chimeric antigen receptor T cells (CAR-Ts) with T-stem cell (TSCM)-like phenotypic characteristics promote sustained antitumor effects. We performed an unbiased and automated high-throughput screen of a kinase-focused compound set to identify kinase inhibitors (KIs) that preserve human TSCM-like CAR-Ts. We identified three KIs UNC10225387B, UNC10225263A and UNC10112761A that combined in vitro increased the frequency of CD45RA+CCR7+TCF1high TSCM-like CAR-Ts from both healthy donors and cancer patients. KIs-treated CAR-Ts showed enhanced antitumor effects both in vitro and in vivo. The KI cocktail maintains TSCM-like phenotype preferentially in CAR-Ts originating from naïve T cells, and promotes dynamic transcriptomic changes without arresting T-cell activation or modulating the chromatin organization. Specific kinases ITK, ADCK3, MAP3K4 and CDK13 targeted by the KI cocktail in a dose-dependent manner are directly associated with the preservation of TSCM-like CAR-Ts. While individual knockdown of these kinases or their combination enriched in TSCM-like CAR-Ts, only CAR-Ts generated in the presence of the KI cocktail show robust expansion and differentiation upon stimulation with tumor cells. Overall, transient pharmacologic inhibition of strategically targeted kinases maintains stem-like features of CAR-Ts and improves their antitumor activity.

2025-01-20 | GSE261127 | GEO

A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells [RNA-Seq]

2025-01-20 | GSE261109 | GEO

A Multi-Kinase Inhibitor Screen Identifies Inhibitors Preserving Stem-Cell-Like Chimeric Antigen Receptor T Cells

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

2025-01-20 | GSE261133 | GEO

chimeric antigen receptor T cells with knockout

Project description:chimeric antigen receptor T cells with knockout

| PRJNA727540 | ENA

Epigenetic profiles of chimeric antigen receptor T cells

Project description:Epigenetic profiles of chimeric antigen receptor T cells

| PRJNA916209 | ENA

Phase I exploratory clinical study of CD276-targeted chimeric antigen receptor T cells for the treatment of solid tumors

Project description:Interventions: experimental group:CD276-targeted chimeric antigen receptor T cells Primary outcome(s): SAE rate Study Design: Single arm

| 2703905 | ecrin-mdr-crc

Haplo / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour

Project description:This clinical trial is an open-label, single-centre, dose escalation, phase I study designed to investigate the safety and tolerability of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects with Relapsed or Refractory Solid Tumour. The study objectives of this phase I study are to determine the safety, activity and the safe dose of haploidentical or allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells given four times weekly in patients with relapsed or refractory solid tumors of different types.

| 2317628 | ecrin-mdr-crc

Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation [expression array]

Project description:Second-generation CD19-targeted chimeric antigen receptors (CAR) have an antigen-binding domain fused to transmembrane, co-stimulatory, and CD3ζ domains. The two CARs with regulatory approval include a CD28 or 4-1BB co-stimulatory domain. While both CARs achieve similar clinical outcomes, biologic differences between the two endodomains have become apparent but not completely understood. The objective is to evaluate gene expression in different mouse CD19-targeted CAR T cells, including m19z, m1928z and m19-musBBz.

2018-07-31 | GSE111641 | GEO

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