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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE246960 | GEO | 2023/11/03

REPOSITORIES: GEO

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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 [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.

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 [scRNA/CITE-seq]

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

| PRJNA1035433 | ENA

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

single cell RNA-sequencing analysis of human SUV39H1-knockout CAR T compared to control CAR T cells (mock) in a xenograft model of lung adenocarcinoma

Project description:We have observed that the inactivation of SUV39H1 enhances 41BBz-CAR T cell long-term persistence, providing protection against tumor relapses and rechallenges in a xenograft mouse model of lung adenocarcinoma. The purpuse of this study is to investigate the transcriptomic differences of lung-infiltrating SUV39H1 knock-out versus mock 41BBz-CAR T cells by single cell RNA sequencing at days 8 and 28 after CAR T cell infusion.

2023-10-31 | GSE244028 | GEO

Effects of SUV39H1 depletion on gene expression in HeLa cells

Project description:HeLa cells were transiently transfected with siRNA against SUV39H1, a histone H3K9 methyltransferase. Several genes were significantly up- or down-regulated. HeLa cells were transiently transfected with siRNA against SUV39H1 or negative control siRNA. Then total RNA was extracted.

2015-08-01 | E-GEOD-59243 | biostudies-arrayexpress

Single cell ATAC-sequencing analysis of human SUV39H1-knockout CAR T compared to control CAR T cells (mock) in a xenograft model of lung adenocarcinoma

Project description:We have observed that the inactivation of SUV39H1 enhances 41BBz-CAR T cell long-term persistence, providing protection against tumor relapses and rechallenges in a xenograft mouse model of lung adenocarcinoma. The purpuse of this study was to profile chromatin accessibility of SUV39H1-deficient compared to mock 41BBz-CAR T cells by single-cell assay for transposase accessible chromatin (scATAC-seq) on FACS-sorted T cells eight days after CAR T cell infusion into the mice.

2023-10-31 | GSE244029 | GEO

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