GEO series

Tumor-site directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors. [human ATACseq]

GSE284616 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 5 samples Submitted 2025/03/16 Platform GPL18573

Summary

The efficacy of Chimeric Antigen Receptor (CAR) T cells against solid tumors is limited by immunosuppressive factors in the tumor microenvironment (TME) including adenosine, which suppresses CAR T cells through activation of the A2A receptor (A2AR). To overcome this, CAR T cells were engineered to express A1 receptor (A1R), a receptor that signals inversely to A2AR. Using murine and human CAR T cells, constitutive A1R overexpression was demonstrated to significantly enhance CAR T cell effector function albeit at the expense of CAR T cell persistence. Through a novel CRISPR/Cas9 “knock-in” approach we demonstrated that CAR T cells engineered to express A1R in a tumor-localized manner, led to enhanced anti-tumor efficacy dependent on the transcription factor IRF8 and was transcriptionally unique when compared to A2AR deletion. This data provides a novel approach for enhancing CAR T cell efficacy in solid tumors and provides proof of principle for site-directed expression of factors that promote effector T cell differentiation.

Published in

Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors

Sek K, Chen AXY, Cole T et al. · Nature communications 2025 · PMID 40610421 · doi:10.1038/s41467-025-59021-9

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Direct links to NCBI, no account and no request form: the whole study as GSE284616_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 5 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1199942 and SRA study SRP552290. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40610421) ↗

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