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Comparison of Transcriptional Profiles of T cells after Activation by TCR and Chimeric Antigen Receptors

ABSTRACT: Comparison of Transcriptional Profiles of T cells after Activation by TCR and Chimeric Antigen Receptors

PROVIDER: PRJNA672932 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12925108_1.fastq.gz	Fastqsanger.gz
	SRR12925108_2.fastq.gz	Fastqsanger.gz
	SRR12925109_1.fastq.gz	Fastqsanger.gz
	SRR12925109_2.fastq.gz	Fastqsanger.gz
	SRR12925110_1.fastq.gz	Fastqsanger.gz

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Comparison of Transcriptional Profiles of T cells after Activation by TCR and Chimeric Antigen Receptors

Project description:Chimeric antigen receptor T (CAR-T) cell therapies for B cell malignancies demonstrate high response rate and durable disease control. However, in the case of solid tumors, CAR-T cells have shown dysfunction ascribed to some intrinsic defects in CAR signaling. Here, we construct a multi-chain chimeric receptor, termed as Synthetic T Cell Receptor and Antigen Receptor (STAR), which incorporates antigen-recognition domain of antibody and engages entire CD3 signaling machinery of T cell receptor (TCR). In multiple solid tumor models, STAR-T cells prominently outperform CAR-T cells without notable toxicity. STAR triggers strong and sensitive TCR-like signaling upon antigen stimulation. We compared the transcriptional profiles of STAR/CAR/TCR-T cells after stimulation for different time points (0, 6, 24, 72 hours), in order to figure out whether signaling difference of these receptors led to distinct gene expression. Our results showd that STAR activation phencopied TCR, while CAR drove a different program, displayed as various pathways related to effector function, cytokine response and cell survival were altered.

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Gene expression profiles of CD4-derived (CAR4) and CD8-derived (CAR8) chimeric antigen receptor T cells after stimulation through the CAR, TCR or both receptors

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