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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy [VDJ-seq]

ABSTRACT: Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy [VDJ-seq]

PROVIDER: PRJNA691020 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13397300_1.fastq.gz	Fastqsanger.gz
	SRR13397300_2.fastq.gz	Fastqsanger.gz
	SRR13397301_1.fastq.gz	Fastqsanger.gz
	SRR13397301_2.fastq.gz	Fastqsanger.gz
	SRR13397302_1.fastq.gz	Fastqsanger.gz

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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy [VDJ-seq]

Project description:While T cell-based immunotherapies have shown promising clinical responses, current cancer treatments are restricted to autologous cellular products due to the risk of graft-versus-host disease (GvHD) by allogeneic cell transfer. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing off-the-shelf allogeneic cellular therapy because they are powerful immune cells targeting a broad range of cancers without causing GvHD. However, current immunotherapies using iNKT cells are impeded by their extremely low number in cancer patients. In this study, we aimed to overcome this limitation by generating a large number of iNKT cells through TCR engineering of human hematopoietic stem cells (HSCs) and differentiation of HSCs to iNKT cells in an in vitro cultured system. Additionally, Chimeric antigen receptor (CAR) engineering and the CRISPR-Cas9 gene editing tool were utilized to enhance the tumor killing efficacy of iNKT cells and eliminate HLA molecules on their surface, making the cellular product suitable for cancer therapy and allogeneic adoptive transfer. Our results demonstrated successful generation of the promising off-the-shelf B cell maturation antigen (BCMA)-CAR engineered iNKT cells for treating multiple myeloma, and the same strategy will be applied to multiple cellular products for treating other cancers.

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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy [RNA-seq]

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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy

Project description:Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy

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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy [RNA-seq]

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Generation of Allogeneic Hematopoietic Stem Cell-Engineered Invariant Natural Killer T cells for Off-the-Shelf Immunotherapy

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

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Gene Regulation by Histone Deacetylase 7 During Invariant Natural Killer T Cell Development

Project description:We have found that the signal-dependent chromatin modulator Histone Deacetylase 7 interacts with and corepresses the signature transcription factor of invariant natural Killer T (iNKT) cells, ZBTB16. This study was designed to determine the global effect on transcription of a gain-of-function mutant of HDAC7 during iNKT cell development and function. Va14/Ja18 T cell receptor transgenic thymocytes and splenocytes, which develop preferentially into iNKT cells, were profiled by RNA-seq with and without expression of a gain-of-functon HDAC7 transgene (HDAC7dP)

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