Summary of Study ST002085

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001324. The data can be accessed directly via it's Project DOI: 10.21228/M8K989 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002085
Study TitleA genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy(Part 1)
Study SummaryChimeric antigen receptor (CAR)-T cell-based immunotherapy for cancer and immunological diseases has made great strides, but it still faces multiple hurdles. Finding the right molecular targets to engineer T cells toward a desired function has broad implications for the armamentarium of T cell-centered therapies. Here, we developed a dead-guide RNA (dgRNA)-based CRISPR activation screen in primary CD8+ T cells, and identified gain-of-function (GOF) targets for CAR-T engineering. Targeted knock-in or overexpression of a lead target, PRODH2, enhanced CAR-T-based killing and in vivo efficacy in multiple cancer models. Transcriptomics and metabolomics in CAR-T cells revealed that augmenting PRODH2 expression re-shaped broad and distinct gene expression and metabolic programs. Mitochondrial, metabolic and immunological analyses showed that PRODH2 engineering enhances the metabolic and immune functions of CAR-T cells against cancer. Together these findings provide a system for identification of GOF immune boosters, and demonstrate PRODH2 as a target to enhance CAR-T efficacy.
Institute
Yale University
Last NameYe
First NameLupeng
Address850 West campus drive
Emaillupeng.ye@yale.edu
Phone2035436568
Submit Date2022-02-12
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2022-02-28
Release Version1
Lupeng Ye Lupeng Ye
https://dx.doi.org/10.21228/M8K989
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Treatment
SA19831020181221_hProdh2_OE_1_M62PRODH2_OE PRODH2
SA19831120181221_hProdh2_OE_5_M62PRODH2_OE PRODH2
SA19831220181221_hProdh2_OE_4_M62PRODH2_OE PRODH2
SA19831320181221_hProdh2_OE_2_M62PRODH2_OE PRODH2
SA19831420181221_hProdh2_OE_3_M62PRODH2_OE PRODH2
SA19831520181221_hProdh2_OE_Vector5_M62Vector_OE Control
SA19831620181221_hProdh2_OE_Vector4_M62Vector_OE Control
SA19831720181221_hProdh2_OE_Vector1_M62Vector_OE Control
SA19831820181221_hProdh2_OE_Vector2_M62Vector_OE Control
SA19831920181221_hProdh2_OE_Vector3_M62Vector_OE Control
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