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ZAP327 signaling domain–driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse models

GSE307776 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/09/14 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples: 3 × 1928z CAR no stimulation vs 3 × 1928z CAR with stimulation vs 3 × 1928ZAP327 CAR no stimulation vs 3 × 1928ZAP327 CAR with stimulationGroups 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
ZAP327 signaling domain-driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse modelsScience translational medicine · 2025
Summary (written by the submitters)
Chimeric antigen receptor (CAR) T-cell therapy has shown impressive clinical responses in the treatment of blood cancers, but high percentages of disease relapse one year after T cell infusion and severe toxicities associated with CAR-T cell therapy remain major issues. Here, we report the construction of CARs with a ZAP-70-derived signaling domain (ZAP327) that enhances therapeutic antitumor activity with increasing in vivo T cell persistence.
Read the full summary ↓
Importantly, ZAP327-driven CAR-T cells markedly reduced cytokine release and expression of T cell exhaustion markers. Mechanistically, we show that the ZAP327 domain tuned down TCR signaling, increased the pools of stem-like memory T cells, and exhibited metabolic features associated with memory T cells by utilizing the oxidative phosphorylation pathway. These results highlight the therapeutic potential of ZAP327-driven CAR-T cells to overcome the limitations of the current CAR-T cell therapies and enhance the potency and persistence of antitumor T cell responses in solid tumors as well.
Published in
ZAP327 signaling domain-driven chimeric antigen receptor generates robust and long-term antitumor immunity in mouse models
Liu X, Zhang J, Chu J et al. · Science translational medicine 2025 · PMID 41370403 · doi:10.1126/scitranslmed.adz0529
This dataset
Open GSE307776 in finder → Find more human RNA-seq datasets →
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.

Series matrix ↓
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 GSE307776_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
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.

Raw reads on ENA ↗

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 PRJNA1327305 and SRA study SRP619193. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41370403) ↗
Study design
3 × 1928z CAR no stimulation vs 3 × 1928z CAR with stimulation vs 3 × 1928ZAP327 CAR no stimulation vs 3 × 1928ZAP327 CAR with stimulation

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
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