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Inosine Induces Stemness Features in HA-CAR-T cells and Enhances Potency

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250443 | GEO | 2023/12/18

REPOSITORIES: GEO

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Inosine Induces Stemness Features in HA-CAR-T cells and Enhances Potency [RNA-seq]

Project description:Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+ HA-CAR-T cells commonly express CD39 and CD73, which mediate proximal steps in Ado generation. Here we sought to enhance HA-CAR-T cell potency by knocking out CD39, CD73 or adenosine receptor 2a (A2aR), but observed only modest effects. In contrast, overexpression of Ado deaminase (ADA-OE), which metabolizes Ado to inosine (INO), induced stemness features and potently enhanced HA-CAR-T functionality. Similarly, and to a greater extent, exposure of HA-CAR-T cells to INO augmented HA-CAR-T cell function and induced hallmark features of T cell stemness. INO induced profound metabolic reprogramming, diminishing glycolysis and increasing oxidative phosphorylation, glutaminolysis and polyamine synthesis, and reprogrammed the epigenome toward greater stemness. Clinical scale manufacturing using INO generated enhanced potency HA-CAR-T cell products meeting criteria for clinical dosing. These results identify INO as a potent modulator of T cell metabolism and epigenetic stemness programming and deliver a new enhanced potency platform for immune cell manufacturing.

2023-12-18 | GSE250442 | GEO

Inosine Induces Stemness Features in HA-CAR-T cells and Enhances Potency [ATAC-seq]

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Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner

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SUV39H1 Ablation Enhances Long-Term CAR-T Function in Solid Tumors.

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

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BLIMP1 and NR4A3 Transcription Factors Reciprocally Regulate Antitumor CAR T-cell Stemness and Exhaustion

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A computational algorithm to predict shRNA potency

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

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FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy [human_FOXO1_TCF7_OE_RNAseq]

Project description:Investigating the transcriptional profile of human FOXO1 or TCF7 overexpressing α-lewisY CAR T cells

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FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy [human_FOXO1_scRNAseq]

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