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Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-seq]

ABSTRACT: Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-seq]

PROVIDER: PRJNA1050260 | ENA |

REPOSITORIES: ENA

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Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

Project description:Adoptive transfer of immune cells expressing chimeric antigen receptors (CARs) is an effective therapy for B-lineage malignancies. However, most patients will relapse and this therapeutic has yet to show strong efficacy in other hematologic or solid tumors. One opportunity for improvement lies in the ability to select or generate T cells that have the highest potential for potent anti-tumor responses and T cell persistence. Here, we dissect the biology of CD8+ CAR T cells by controlling whether the T cell has encountered cognate TCR antigen prior to CAR generation. We find that prior antigen experience influences multiple aspects of in vitro and in vivo CAR T cell functionality, boosting effector function and leukemia clearance in the setting of limiting target antigen density. However, this comes at the expense of proliferative capacity, resistance to dysfunction, and clearance of wildtype leukemia in the setting of limiting CAR+ cell dose. Epigenetic and transcriptomic comparisons of these cell populations uncover that modulation of the Runx2 transcription factor differentially impacts CAR T cell functionality depending on prior cell state. Collectively, our data demonstrate that prior antigen experience status determines functional attributes of a CAR T cell, as well as amenability to functional enhancement by transcription factor modulation.

2024-11-14 | GSE281486 | GEO

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

Project description:Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

| PRJNA1184132 | ENA

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

Project description:Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

| PRJNA1050258 | ENA

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-Seq]

2024-11-14 | GSE281588 | GEO

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-seq]

2024-11-10 | GSE249733 | GEO

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [RNA-seq]

2024-11-10 | GSE249732 | GEO

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [RNA-seq]

Project description:Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [RNA-seq]

| PRJNA1050261 | ENA

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-Seq]

Project description:Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response [ATAC-Seq]

| PRJNA1184767 | ENA

Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

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

2024-11-11 | GSE249734 | GEO

Transfer of antigen target into CAR T cells via trogocytosis

Project description:To characterize transfer of molecules from target cells into CAR T cells via trogocytosis we cultured NALM-6 leukemia cell line expressing a CD19-mCherry fusion protein with CAR T cells. NALM6-CD19-mCherry were loaded with heavy amino acid and cocultured with CAR T cells for 1 hour. CAR T cells were next sorted into two fractions, mCherry-positive (TrogPos), and -negative (TrogNeg). Proteomics analysis revealed the presence of targeted antigen (CD19) in the TrogPos only.

2019-03-29 | PXD012833 | Pride

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