Ye, Lupeng; Park, Jonathan J.; Peng, Lei; Yang, Quanjun; Chow, Ryan D.; Dong, Matthew B.; Lam, Stanley Z.; Guo, Jianjian; Tang, Erting; Zhang, Yueqi; Wang, Guangchuan; Dai, Xiaoyun; Du, Yaying; Kim, Hyunu R.; Cao, Hanbing; Errami, Youssef; Clark, Paul; Bersenev, Alexey; Montgomery, Ruth R.; Chen, Sidi published the artcile< A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy>, Category: esters-buliding-blocks, the main research area is breast cancer proline metabolism CAR T therapy CRISPR; CAR-T; PRODH2; T cell CRISPR activation screen; T cell GOF screen; antitumor efficacy; dead-guide RNA; metabolism; mitochondria; proline metabolism.
Chimeric antigen receptor (CAR)-T cell-based immunotherapy for cancer and immunol. diseases has made great strides, but it still faces multiple hurdles. Finding the right mol. 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 knockin 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 reshaped broad and distinct gene expression and metabolic programs. Mitochondrial, metabolic, and immunol. 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.
Cell Metabolism published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (Ccnb1i.p.1). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Category: esters-buliding-blocks.
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Ester – an overview | ScienceDirect Topics