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RNA-Seq based gene expression profiling of naïve B-cells from CTCFfl/+ CD19-Creki/+ mice.

ABSTRACT: RNA-Seq based gene expression profiling of naïve B-cells from CTCFfl/+ CD19-Creki/+ mice.

PROVIDER: PRJNA856500 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20016460.fastq.gz	Fastqsanger.gz
	SRR20016461.fastq.gz	Fastqsanger.gz
	SRR20016462.fastq.gz	Fastqsanger.gz

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RNA-Seq based gene expression profiling of naïve B-cells from CTCFfl/+;CD19-Creki/+ mice.

Project description:The goal of this study was to establish the gene expression profile of naïve B-cells from CTCFfl/+;CD19-Creki/+ mice, using RNA-seq technology.

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ChIP-Seq based CTCF binding profiling of naïve B-cells from CTCFfl/fl CD19-Creki/+ or CTCFfl/+ CD19-Creki/+ mice.

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Project 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 naïve precursors. CD8+CD62L+CD45RA+ naïve 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-3β 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.

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