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Systematic discovery of CRISPR-boosted CAR T cell immunotherapies

GSE266618 Homo sapiens (human) RNA-seq (gene expression) 60 samples Submitted 2025/07/22 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 60 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
60 samples: 20 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Systematic discovery of CRISPR-boosted CAR T cell immunotherapiesNature · 2025
Summary (written by the submitters)
CAR T cell therapy has shown remarkable success in treating blood cancers, but CAR T cell dysfunction is a common cause of treatment failure. Here we present CELLFIE, a CRISPR screening platform for enhancing CAR T cells across multiple clinical objectives. We performed genome-wide screens in human primary CAR T cells with readouts capturing key aspects of T cell biology, including proliferation, target cell recognition, activation, apoptosis and fratricide, and exhaustion.
Read the full summary ↓
Screening hits were prioritized using a new in vivo CROP-seq method in a xenograft model of human leukemia, establishing several gene knockouts that boost CAR T cell efficacy. Most notably, we discovered RHOG knockout as a potent and unexpected CAR T cell enhancer, both individually and together with FAS knockout, which was validated across multiple in vivo models, CAR designs, and patient-derived cells. Demonstrating the versatility of the CELLFIE platform, we also conducted combinatorial CRISPR screens to identify effective knockout pairs, and saturation base editing screens to characterize RHOG variants. In summary, we discovered, validated, and biologically characterized CRISPR-boosted CAR T cells that outperform standard CAR T cells in widely used benchmarks, establishing a foundational resource for optimizing cell-based immunotherapies.
Published in
Systematic discovery of CRISPR-boosted CAR T cell immunotherapies
Datlinger P, Pankevich EV, Arnold CD et al. · Nature 2025 · PMID 40993398 · doi:10.1038/s41586-025-09507-9
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE266618_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1107960. Searching any of these in the dataset finder brings you back here.

Study design
20 conditions, mostly in triplicate
CD4, 0h, SafeHarbor, CART0077_D ×3 CD4, 0h, RHOG, CART0077_D ×3 CD8, 0h, SafeHarbor, CART0077_D ×3 CD8, 0h, RHOG, CART0077_D ×3 CD4, 24h, SafeHarbor, CART0077_D ×3 CD4, 24h, RHOG, CART0077_D ×3 CD8, 24h, SafeHarbor, CART0077_D ×3 CD8, 24h, RHOG, CART0077_D ×3 +12 more

Supports a between-group comparison across 60 samples.

How we read this: 20 replicated groups read from 60 sample titles; they account for 60 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 20 more — browse all 60 samples with per-sample file links →

Datasets on a similar topic

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