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TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody induces tumor regression through profound tumor microenvironment remodeling and strong antitumor adaptive immune response [RNA-seq]

GSE259380 Mus musculus (mouse) RNA-seq (gene expression) 149 samples Submitted 2024/07/30 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 149 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
Mus musculus (mouse)
Samples
149 samples: 9 conditions, mostly with about 10 replicates eachGroups 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
TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironmentJournal for immunotherapy of cancer · 2024
Summary (written by the submitters)
By their selective infection or replication into tumors, oncolytic viruses trigger profound modifications of tumor immune microenvironment with a massive infiltration and activation of T cells. This tumor warming up can be further amplified by the local delivery of powerful immunomodulatory molecules encoded into virus’ genome. Those properties are particularly of interest for tumor poorly infiltrated or infiltrated with anergic T cells to reverse patient’s unresponsiveness to immune checkpoint inhibitors (ICI).
Read the full summary ↓
TG6050 is a new oncolytic vaccinia virus encoding single-chain human Interleukin-12 (hIL-12) and full length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. Replication, oncolysis, selectivity, transgenes expression and functionality of TG6050 were characterized in vitro. Virus and IL-12 pharmacokinetics, antitumoral activities (alone or combined with ICI), and mechanism of action (MOA) were investigated in “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. MOA was deciphered by monitoring both systemic and tumor immune responses, and tumor transcriptome analyses. Finally, TG6050 safety after repeated intravenous administrations was evaluated in cynomolgus monkeys and special attention was paid to the level of circulating IL-12 potentially associated with toxic effects. In vitro or in vivo replication of TG6050 in tumor cells allows local expression of functional IL-12 and @CTLA-4. The expression of transgenes, together with the virus replication, translated into an antitumoral activity in both “cold and “hot” tumor murine models that was further amplified by combination with ICI. Analysis of tumor microenvironment (TME) after TG6050 treatment showed an increase of interferon gamma, CD8+ T cells, M1/M2 macrophages ratio and a drastic decrease of regulatory T cells. Those local modifications were observed together with an enhanced systemic and specific antitumor adaptive immune response. In toxicology studies, the virus did not produce any observable adverse effects in cynomolgus monkeys. Conclusions: TG6050 allows the delivery of functional IL-12 and @CTLA-4 into tumor resulting in an excellent antitumor activity along with a shift towards an inflamed TME, and a boost of the systemic antitumor T-cells. Toxicological studies in macaques demonstrated the safety of TG6050. Together these results paved the way for clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926).
Published in
TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment
Azar F, Deforges J, Demeusoit C et al. · Journal for immunotherapy of cancer 2024 · PMID 39060022 · doi:10.1136/jitc-2024-009302
This dataset
Open GSE259380 in finder → Find more mouse 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 GSE259380_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 PRJNA1081387 and SRA study SRP492064. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39060022) ↗
Study design
9 conditions, mostly with about 10 replicates each
untreated CT26 tumors D11 ×10 COPTG19289-treated CT26 tumors D11 ×10 COPTG19859-treated CT26 tumors D11 ×10 untreated CT26 tumors D15 ×10 COPTG19289-treated CT26 tumors D15 ×10 COPTG19859-treated CT26 tumors D15 ×10 untreated CT26 tumors D17 ×10 COPTG19289-treated CT26 tumors D17 ×10 +61 more

Supports a between-group comparison across 89 samples.

How we read this: 9 replicated groups read from 149 sample titles; they account for 89 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

+ 109 more — browse all 149 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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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.