GEO series

Multimodal single-cell profiling reveals the enhanced antitumor activity of FGFR4/CD276 BiCisCAR T cells in rhabdomyosarcoma

GSE228127 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2024/05/23 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 12 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Homo sapiens (human)
Topic: Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples: 12 samples
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: CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcomaNature communications · 2024

Summary (written by the submitters)

We have generated a clinical grade CAR T targeting FGFR4 with a CD8 hinge and transmembrane domain (HTM) and a 4-1BB co-stimulatory domain (CSD) that is currently being developed for a clinical trial at the NCI. This standard FGFR4-CAR demonstrated potency in low burden RMS disease but has a more modest effect for bulky disease in RMS orthotopic model.

Read the full summary ↓

Thus, we developed optimized FGFR4-CARs by modification of HTM or CSD to improve its efficacy. However, these modified FGFR4-CARs, even FGFR4.28HTM.28z CAR were unable to eradicate solid tumors in an more aggressive RMS559 model. CAR T cells targeting another cell surface protein CD276, a direct target of the RMS core-regulatory transcription factor MYOD1 is potent and effective, also could not eradicate the tumor. Therefore, we engineered a bicistronic CAR (BiCisCAR) to target both FGFR4 and CD276, with CD28 and 4-1BB CSDs, respectively, which showed remarkable and rapid tumor eradication compared with either single CAR alone. Here, we utilized a multimodal approach including simultaneous protein and transcriptome measurement at single cell level to characterize each FGFR4 or CD276 CAR T-cell infiltrating in RMS orthotopic xenografts. This assay further determined the molecular basis of superior antitumor effect of FGFR4.28HTM.28z-CD276.8HTM.BBz BiCisCAR T cells compared with other CARs.

Published in

CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcoma

Tian M, Wei JS, Cheuk AT et al. · Nature communications 2024 · PMID 39043633 · doi:10.1038/s41467-024-50251-x

This dataset

Open GSE228127 in finder → Find more human RNA-seq datasets → Soft tissue sarcoma landscape →

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 GSE228127_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA948361 and SRA study SRP429096. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39043633) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 12 more — browse all 12 samples with per-sample file links →

More Soft tissue sarcoma datasets

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GSE314949 RNA Seq of rhabdomyosarcoma cells with sgRNA targeting oncofusion interacting proteins 30 samples same disease briefing · shares rhabdomyosarcoma
GSE279954 mRNA/sRNA Co-Sequencing Reveals Multiple New Targeted Therapy Candidates in Rhabdomyosarcoma 26 samples same disease briefing · shares rhabdomyosarcoma
GSE292872 FANCM is Required for the PAX3::FOXO1-Driven Oncogenic Program in Rhabdomyosarcoma [RNA-Seq] 21 samples same disease briefing · shares rhabdomyosarcoma
GSE202614 TLE3 function in rhabdomyosarcoma tumor xenografts. 20 samples same disease briefing · shares rhabdomyosarcoma
GSE240287 RNA-sequencing of matched samples from rhabdomyosarcoma samples, obtained before therapy and mid-treatment resection 18 samples same disease briefing · shares rhabdomyosarcoma
GSE286950 PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma 16 samples same disease briefing · shares rhabdomyosarcoma

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.