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Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE245187 | GEO | 2023/10/26

REPOSITORIES: GEO

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Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function.

Project description:Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies.SignificanceT cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells. See related article by López-Cobo et al., p. 120. This article is featured in Selected Articles from This Issue, p. 5.

| S-EPMC10880746 | biostudies-literature

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [ATAC-Seq]

Project description:Comparing genome accessibility profiles (ATACseq) of WT and SUV39H1-edited CAR T cells

2023-10-27 | GSE245186 | GEO

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [RNA-Seq]

Project description:Comparing transcriptional profiles (RNAseq) of WT and SUV39H1-edited CAR T cells

2023-10-27 | GSE245184 | GEO

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [scRNA/CITE-seq]

Project description:Single cell gene expression profile of WT and SUV39H1-edited CAR T cells at pre-infusion (Day 0), day 9 and day 16 post infusion in tumor (NALM6) bearing NSG mice

2023-11-03 | GSE246960 | GEO

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function

Project description:Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function

| PRJNA1027320 | ENA

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [RNA-Seq]

Project description:Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [RNA-Seq]

| PRJNA1027329 | ENA

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [ATAC-Seq]

Project description:Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [ATAC-Seq]

| PRJNA1027332 | ENA

Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [scRNA/CITE-seq]

Project description:Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function [scRNA/CITE-seq]

| PRJNA1035433 | ENA

DOT1L Inhibits SIRT1 and SUV39H1-Mediated H3K9 Modification to Maintain Gene Expression

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

2015-03-30 | GSE61022 | GEO

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

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

2023-10-30 | GSE244032 | GEO

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