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BiTE® Molecule vs. CAR-T targeting FLT3 in AML: How Positive Co-Stimulation Tips the Scale

GSE298033 Homo sapiens (human) RNA-seq (gene expression) 15 samples Submitted 2026/02/25 Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 15 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)
Topic
Acute myeloid leukemiaThis series is part of our curated briefing on it.
Samples
15 samples: 10 × human T cells from bone marrow of NSG mice, CAR, vs 5 × human T cells from bone marrow of NSG mice, BiTE,Groups 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
FLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustionBlood advances · 2026
Summary (written by the submitters)
T-cell-based immunotherapies have revolutionized treatment paradigms in B-cell malignancies, yet their translation to acute myeloid leukemia (AML) has been hindered by a scarcity of tumor-restricted antigens and the risk of on-target off-leukemia toxicity. FLT3 has emerged as a promising therapeutic target with limited expression in healthy hematopoietic tissues.
Read the full summary ↓
Here, we perform a head-to-head preclinical comparison of a FLT3-directed bispecific T-cell engager (BiTE® molecule) and second-generation FLT3-specific chimeric antigen receptor (CAR) T cells. Both approaches induced potent cytotoxicity against AML cell lines and primary patient-derived blasts while sparing healthy hematopoietic stem and progenitor cells. Despite similar short-term efficacy, prolonged antigen exposure demonstrated progressive functional decline and metabolic exhaustion; however, CAR T cells maintained cytotoxic capacity and proliferative potential over time. In AML xenograft models, CAR T cells achieved superior tumor control, prolonged survival, and greater T-cell infiltration than BiTE® molecule-treated counterparts. Transcriptomic profiling of T cells recovered from bone marrow further revealed a distinct exhaustion-associated gene signature in BiTE®-redirected T cells. Importantly, provision of CD86-mediated co-stimulation significantly enhanced the antitumor activity of BiTE®-redirected T cells in vitro and in vivo. These findings establish FLT3 as a viable and selective immunotherapeutic target in AML and underscore the functional and transcriptional differences between BiTE® molecule-redirected T cells and CAR T cells. Moreover, they reveal the critical role of co-stimulatory signaling in sustaining the efficacy of T-cell-based therapies in vivo, offering a rational path for improving T-cell redirection strategies in myeloid malignancies.
Published in
FLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion
Rohrbacher L, Nixdorf D, Stadler H et al. · Blood advances 2026 · PMID 41324594 · doi:10.1182/bloodadvances.2025018168
This dataset
Open GSE298033 in finder → Find more human RNA-seq datasets → Acute myeloid leukemia 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 GSE298033_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 PRJNA1267134 and SRA study SRP587272. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41324594) ↗
Study design
10 × human T cells from bone marrow of NSG mice, CAR, vs 5 × human T cells from bone marrow of NSG mice, BiTE,

Supports a between-group comparison across 15 samples.

How we read this: 2 replicated groups read from 15 sample titles; they account for 15 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
More Acute myeloid leukemia datasets

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