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Gene expression profiles of CAR-T cells engineered with chimeric cytokine receptors to induce JAK-STAT signaling

GSE255145 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2024/03/24 Platform GPL24676
Summary
The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is insufficient in most cancers. However, enhancing the antitumor T cell response inevitably increases the risk of cytokine release syndrome associated with monocyte-derived IL-6 secretion. In this study, we developed a chimeric cytokine receptor consisting of the extracellular domains of GP130 and IL6RA linked to the transmembrane and cytoplasmic domain of IL-7R mutant (insertion of PPCL) (G6/7R). We also generated a modified receptor with the M452L mutation in the IL7R cytoplasmic domain (G6/7R-M452L). CAR-T cells with G6/7R or G6/7R-M452L efficiently absorbed monocyte-derived IL-6 and induced a superior therapeutic response compared to conventional CAR-T cells. Our strategy can be broadly applied to CAR-T cell therapy to enhance its efficacy and safety, irrespective of the target antigen.
Published in
Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells
Yoshikawa T, Ito Y, Wu Z et al. · Cell reports. Medicine 2024 · PMID 38670095 · doi:10.1016/j.xcrm.2024.101526
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Direct links to NCBI, no account and no request form: the whole study as GSE255145_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1073839 and SRA study SRP488417. Searching any of these in the dataset finder brings you back here.

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