Ontology highlight
ABSTRACT:
PROVIDER: PRJNA542504 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9045864_1.fastq.gz | Fastqsanger.gz | |||
| SRR9045864_2.fastq.gz | Fastqsanger.gz | |||
| SRR9045865_1.fastq.gz | Fastqsanger.gz | |||
| SRR9045865_2.fastq.gz | Fastqsanger.gz | |||
| SRR9045866_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:Compared the gene expression profiles between the PTL-Her2-CAR-T cells and Her2-CAR-T cells isolated from tumor tissues
| PRJNA542661 | ENA
Project description:Purpose: To compare cell states between control Her2-BBz and JUN-overexpression Her2-BBz human CAR T cells in a mouse model of osteosarcoma. Methods: 8-week old NSG mice were implanted with 1 million 143B osteosarcoma tumor cells intramuscularly in the right leg. 14 days post tumor implantation, mice were infused intravenously with 10 million human CAR+ T cells via tail vein injection. Before T cell transfer, mice were randomized for tumor size and treated with either control Her2-BBz or JUN-overexpressing Her2-BBz CAR T cells. T cells were 70% CAR+ at infusion for both groups. 14 days post T cell treatment (day 28 post tumor engraftment), 6 mice per group were euthanized, solid tumor tissue was collected, mechanically dissociated, and single cell suspensions were labeled with human-CD45 antibody and viability dye. Live hCD45+ tumor-infiltrating lymphocytes were sorted from each tumor and 6 samples were pooled for each group. ~35,000-40,000 sorted live cells (counted post sort) for each group were delivered to the Stanford Functional Genomics Facility for 3' single-cell RNA-sequencing on the 10X Genomics platform. Results: We found that substantially more JUN-overexpressing Her2-BBz CAR T cells were within the G2/M and S phases of the cell cycle than control Her2-BBz CAR T cells, consistent with increased in vivo proliferation of JUN-Her2-BBz CAR T cells. Furthermore, JUN-Her2-BBz CAR T cells also demonstrated a more activated transcriptional program (as measured by IL2RA and CD38), while many exhaustion-associated genes were downregulated (PDCD1, BTLA, TIGIT, CD200, ENTPD1, NR4A2) compared to control Her2-BBz CAR T cells. Finally, a small cluster of cells characterized by high IL7R expression (IL7R+ KLF2+ CD27+ TCF7+ SELL+) was apparent in JUN-overexpressing but not in control Her2-BBz CAR T cells, consistent with maintenance of a memory-like population capable of self-renewal. Conclusions: This study provides insights into cell states that could explain the improved efficacy of JUN-overexpression Her2-BBz CAR T cells compared to control Her2-BBz CAR T cells in a mouse model of osteosarcoma.
2019-10-01 | GSE136805 | GEO
Project description:T cell exhaustion and metabolic dysfunction induced by chronic antigen stimulation within the tumor microenvironment represent formidable obstacles in CAR T cell therapy for solid tumors. Previously, we developed a method to convert effector/exhausted CAR T cells that emerge from repeated antigen stimulation into stem cell memory-like CAR T (termed CAR-iTSCM) cells. These CAR-iTSCM cells exhibit expression of early memory markers and enhanced mitochondrial metabolism after quiescence under culture conditions containing IL-7, CXCL12, and the NOTCH-ligand. However, we noticed that this strategy was effective for CD19-CAR used for blood cancers, but not for HER2 CAR commonly used to treat solid tumors, due to tonic CAR signals. In this study, we developed a new culture condition for CAR iTSCM cells suitable for HER2 CAR and elucidated the mechanism of induction of stemness and mitochondrial fitness. We found that short-term resting condition with IL-7, CXCL12, and pan-tyrosine kinase inhibitor, Dasatinib can induce stem-like CAR T cells at the epigenetic level and enhance mitochondrial metabolism. We identified FOXO1 as a critical regulator in the process of epigenetic and metabolic reprogramming, and anti-tumor activity. We found that overexpression of FOXO1 leads to enhanced mitochondrial metabolism, efficient CAR T cell expansion, and potent anti-tumor effects through epigenetic modifications. These findings suggest that regulating the transcriptional activity of FOXO1 is a promising strategy for engineering effective CAR T cells for treating solid tumors. In this analysis, we aimed to investigate the effects of the resting conditions (IL-7+CXCL12+IGF-I +Dasatinib) and FOXO1 overexpression on the epigenetic profiles in 4-1BB-based HER2 CAR T cells which exhibit tonic signals-induced exhaustion hallmarks.
2023-11-21 | GSE247336 | GEO
Project description:T cell exhaustion and metabolic dysfunction induced by chronic antigen stimulation within the tumor microenvironment represent formidable obstacles in CAR T cell therapy for solid tumors. Previously, we developed a method to convert effector/exhausted CAR T cells that emerge from repeated antigen stimulation into stem cell memory-like CAR T (termed CAR-iTSCM) cells. These CAR-iTSCM cells exhibit expression of early memory markers and enhanced mitochondrial metabolism after quiescence under culture conditions containing IL-7, CXCL12, and the NOTCH-ligand. However, we noticed that this strategy was effective for CD19 CAR used for blood cancers, but not for HER2 CAR commonly used to treat solid tumors, due to tonic CAR signals. In this study, we developed a new culture condition for CAR iTSCM cells suitable for HER2 CAR and elucidated the mechanism of induction of stemness and mitochondrial fitness. We found that short-term resting condition with IL-7, CXCL12, and pan-tyrosine kinase inhibitor, Dasatinib can induce stem-like CAR T cells at the epigenetic level and enhance mitochondrial metabolism. We identified FOXO1 as a critical regulator in the process of epigenetic and metabolic reprogramming, and anti-tumor activity. We found that overexpression of FOXO1 leads to enhanced mitochondrial metabolism, efficient CAR T cell expansion, and potent anti-tumor effects through epigenetic modifications. These findings suggest that regulating the transcriptional activity of FOXO1 is a promising strategy for engineering effective CAR T cells for treating solid tumors. In this analysis, we aimed to investigate the effects of the resting conditions (IL-7+CXCL12+IGF-I +Dasatinib) on the transcriptomic profiles in 4-1BB-based HER2 CD8+ CAR T cells which exhibit tonic signals-induced exhaustion hallmarks.
2023-11-21 | GSE247465 | GEO
Project description:T cell exhaustion and metabolic dysfunction induced by chronic antigen stimulation within the tumor microenvironment represent formidable obstacles in CAR T cell therapy for solid tumors. Previously, we developed a method to convert effector/exhausted CAR T cells that emerge from repeated antigen stimulation into stem cell memory-like CAR T (termed CAR-iTSCM) cells. These CAR-iTSCM cells exhibit expression of early memory markers and enhanced mitochondrial metabolism after quiescence under culture conditions containing IL-7, CXCL12, and the NOTCH-ligand. However, we noticed that this strategy was effective for CD19 CAR used for blood cancers, but not for HER2 CAR commonly used to treat solid tumors, due to tonic CAR signals. In this study, we developed a new culture condition for CAR iTSCM cells suitable for HER2 CAR and elucidated the mechanism of induction of stemness and mitochondrial fitness. We found that short-term resting condition with IL-7, CXCL12, and pan-tyrosine kinase inhibitor, Dasatinib can induce stem-like CAR T cells at the epigenetic level and enhance mitochondrial metabolism. We identified FOXO1 as a critical regulator in the process of epigenetic and metabolic reprogramming, and anti-tumor activity. We found that overexpression of FOXO1 leads to enhanced mitochondrial metabolism, efficient CAR T cell expansion, and potent anti-tumor effects through epigenetic modifications. These findings suggest that regulating the transcriptional activity of FOXO1 is a promising strategy for engineering effective CAR T cells for treating solid tumors. In this analysis, we aimed to investigate the effects of FOXO1WT overexpression on the transcriptomic profiles in 4-1BB-based HER2 CD8+ CAR T cells which exhibit tonic signals-induced exhaustion hallmarks.
2023-11-21 | GSE247471 | GEO
Project description:Chimeric Antigen Receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies. However, it is limited to individualized cell therapy and faces challenges, including high costs, extended preparation time, and limited efficacy against solid tumors. Here, we generated circular RNAs (circRNAs) encoding Chimeric Antigen Receptor (CAR) transmembrane proteins, referred to as circRNACAR, which mediated remarkable tumor killing in both T cells and macrophages. In addition, macrophages exhibited efficient phagocytosis of tumor cells and pro-inflammatory polarization induced by circRNACAR in vitro. We demonstrated that circRNACAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), significantly inhibited tumor growth, improved survival rates and induced a pro-inflammatory tumor microenvironment in mice. Importantly, the combination of circRNAAnti-HER2-CAR and circRNA-based cancer vaccines encoding the corresponding transmembrane HER2 antigen, termed circRNAHER2, exhibited synergistically enhanced anti-tumor activity. Notably, we found that circRNACAR could boost the level of circRNAHER2-elicited antibodies, which could mediate effective killing of HER2+ tumor cells by macrophages, indicating the potential of vaccination-elicited antibodies in developing novel immunotherapy. This proof-of-concept study demonstrated that the combination of circRNA-based in vivo CAR and vaccines, termed in vivo CAR-VAC, holds the potential to become an upgraded off-the-shelf immunotherapy, and also sheds light on the huge potential of vaccination-elicited antibodies in cancer immunotherapy.
2024-05-22 | GSE268105 | GEO
Project description:Human CD8+ T cells were transduced with lentivirus encoding for HER2-CAR-2A-GFP or HER2-CAR-2A-BATF3. T cells were either only stimulated once after thawing (acute stimulation) or repeatedly stimulated with HER2+ SKBR3 cells at a 1:2 effector to target (E:T) ratio every 3 days (chronic stimulation).
2023-05-24 | GSE218987 | GEO
Project description:Transcriptomic analysis of tumor tissues isolated from animals bearing F9 teratocarcinoma. 129Sv mice were challenged with F9 tumor cells and, when tumors were palpable, mice were treated with EDA CAR-T s (a mixture of 1×107 CD4+ and 2×106 CD8+ CAR-T cells)or left untreated. 14 days after adoptive transfer, RNA was isolated from tumors for their transcriptomic analysis.
2022-08-10 | GSE204887 | GEO
Project description:To further development of different gene expression between the PTL-Her2-CAR-T cells (knockdown of PD-1, Tim-3, Lag-3 by shRNA-clusters in Her2-CAR-T cells) and Her2-CAR-T cells, we have employed whole genome microarray expression profiling as a discovery platform.
2019-09-23 | GSE131107 | GEO
Project description:Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.
| 2210681 | ecrin-mdr-crc