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GSE68003
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical grade tumor-redirected TSCM cells starting from nave precursors. CD8+CD62L+CD45RA+ nave T cells enriched by streptamer-based serial positive selection were activated by CD3/CD28 engagement in the presence of IL-7, IL-21 and the glycogen synthase-3 inhibitor TWS119, and genetically engineered to express a CD19-specific chimeric antigen receptor (CD19-CAR). These conditions allowed for the generation of CD19-CAR modified TSCM cells that were phenotypically, functionally and transcriptomically equivalent to their naturally occurring counterpart. Compared with T cell products currently under clinical investigation, CD19-CAR modified TSCM cells exhibit enhanced metabolic fitness, persistence and anti-tumor activity against systemic acute lymphoblastic leukemia xenografts. Based on these findings, we have initiated a phase 1 clinical study to evaluate the activity of CD19-CAR modified TSCM in patients with B-cell malignancies refractory to prior allogeneic hematopoietic stem cell transplantation.
Publication Title
Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6633 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathway–specific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 304 Downloadable Samples
- Affymetrix Genome-Wide Human SNP 6.0 Array (genomewidesnp6), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 538 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 534 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 526 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 524 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 521 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 513 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 509 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To identify patterns of drug-induced gene modulation that occur across different cell types, we measured gene expression changes across NCI-60 cell lines after exposure to 15 anticancer agents. The results were integrated into a database and set of interactive analysis tools, the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), intended to allow exploration of gene expression modulation, including by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across drugs and cell types and uncovered cell signaling pathwayspecific gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses, utilizing the NCI TPW to assess drug-induced expression changes in genes associated with immune function and epithelial-mesenchymal transition, and to identify candidate biomarkers for drug activity. The NCI TPW provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to anticancer drugs.
Publication Title
The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Sample Metadata Fields
Specimen part
View Samples