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Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicity

GSE278512 Homo sapiens (human) RNA-seq (gene expression) 45 samples Submitted 2024/10/05 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 45 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
45 samples: 15 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
Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicityImmunity · 2024
Summary (written by the submitters)
Major challenges of CAR-T cell therapy include poor antigen sensitivity and cell persistence. Here we report a solution to these issues by exploiting CAR phase separation. We found that incorporation of an engineered CD3e motif, EB6I, to the conventional 28Z or BBZ CAR induced self-phase separation through cation-π interactions. EB6I CAR can form a mature immunological synapse with CD2 corolla to transduce efficient antigen and costimulatory signaling, while its tonic signaling remains at low levels.
Read the full summary ↓
Functionally, EB6I CAR-T cells exhibited improved signaling and cytoxicity against low-antigen tumor and persistent tumor killing function. In multiple primary and relapsed murine tumor models, EB6I CAR-T cells exerted better antitumor functions than conventional CAR-T cells against blood and solid cancers. This study thus unveils a new CAR engineering strategy to improve CAR-T cell immunity by leveraging molecular condensation and signaling integration.
Published in
Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicity
Xu X, Chen H, Ren Z et al. · Immunity 2024 · PMID 39609126 · doi:10.1016/j.immuni.2024.11.005
This dataset
Open GSE278512 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 GSE278512_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 PRJNA1167671 and SRA study SRP535924. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39609126) ↗
Study design
15 conditions, mostly in triplicate
EB6I28Z CAR-T cells 1st round ×3 EB6I28Z CAR-T cells 2nd round ×3 EB6I28Z CAR-T cells 3rd round ×3 EB6I28Z CAR-T cells 5th round ×3 EB6I28Z CAR-T cells rest ×3 E28Z CAR-T cells 1st round ×3 E28Z CAR-T cells 2nd round ×3 E28Z CAR-T cells 3rd round ×3 +7 more

Supports a between-group comparison across 45 samples.

How we read this: 15 replicated groups read from 45 sample titles; they account for 45 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

+ 5 more — browse all 45 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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