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NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [scRNA-Seq]

ABSTRACT: NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [scRNA-Seq]

PROVIDER: PRJNA1008193 | ENA |

REPOSITORIES: ENA

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NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication

Project description:NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication

| PRJNA1008188 | ENA

NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [RNA-Seq]

Project description:Chimeric antigen receptor (CAR)-T cell therapy targeting human CD19 have demonstrated clinical efficacy against B-cell malignancies. However, CAR-T cell therapy's efficacy against solid tumors is limited due to factors like low tumor-associated antigens, infiltration rate, and T cell exhaustion. We have shown that deleting NR4a genes in CAR-T cells prevents T cell exhaustion and improved their therapeutic effects on solid tumors in a mouse model. To further explore this for human, we deleted all three NR4a family factors in CAR-T cells that recognize Epidermal Growth Factor Receptor type 2 (HER2) using the CRISPR/Cas9 system. These modified CAR-T cells (NR4a-TKO CAR-T) exhibited resistance to exhaustion, increased tumor-killing activity, and higher efficacy in tumor regression and survival rate in a human lung carcinoma model in mice. The enhanced therapeutic effects were associated with increased cytokine expression, reduced exhaustion-related gene expression, and improved persistence within tumors. We propose that targeting NR4a could be a promising strategy for developing superior CAR-T cells against solid tumors.

2024-08-28 | GSE241456 | GEO

NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [scRNA-Seq]

2025-08-01 | GSE241457 | GEO

NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [RNA-Seq]

Project description:NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [RNA-Seq]

| PRJNA1008189 | ENA

NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication

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

2024-08-30 | GSE241458 | GEO

Nr4a transcription factors limit CAR-T cell function in solid tumors

Project description:Nr4a transcription factors limit CAR-T cell function in solid tumors

| PRJNA509664 | ENA

Nr4a transcription factors limit CAR-T cell function in solid tumors [RNA-Seq]

Project description:Nr4a transcription factors limit CAR-T cell function in solid tumors [RNA-Seq]

| PRJNA509668 | ENA

Nr4a transcription factors limit CAR-T cell function in solid tumors [ATAC-Seq]

Project description:Nr4a transcription factors limit CAR-T cell function in solid tumors [ATAC-Seq]

| PRJNA509426 | ENA

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade

Project description:We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we developed clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduced tumor burden, prolonged survival, remodeled the TME, increased intratumoral T cell and natural killer (NK) cell infiltration, and induced epitope spreading. CAR-M therapy protected against antigen-negative relapse in a T cell dependent fashion, confirming long-term anti-tumor immunity. In HER2+ solid tumors resistant to anti-PD1(aPD1) monotherapy, the combination of CAR-M and aPD1 significantly improved tumor growth control, survival, and remodeling of the TME. These results demonstrate synergy between CAR-M and T cell checkpoint blockade and provide a strategy to enhance response to aPD1 therapy for patients with non-responsive tumors.

2024-11-20 | GSE275417 | GEO

Gene expression profiles of wild type and Nr4a-triple knockout (Nr4a-TKO) Tnaive and iTreg 3 h

Project description:In this study, we investigated the roles of Nr4a family transcription factors in Th and Treg cell differentiation from Tnaive cells. Nr4a factors were found to promote Treg cell differentiation and repress Th1 and Th2 differentiation. During Treg cell differentiation, all Nr4a factors are transiently induced in Tnaive cells immediately after TCR stimulation, whereby they mediate epigenetic changes directly or by cooperating with other transcription factors. To reveal Nr4a factors' mediated transcrptional events, we analyzed gene expression of wild type and Nr4a-tripple knockout (Nr4a-TKO) Tnaive and iTreg cells by microarray analysis.

2020-07-08 | GSE153926 | GEO

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