Fig. 1: Targeting interleukin 13 receptor subunit alpha 2 (IL-13Rα2) for immunotoxin therapy in diffuse intrinsic pontine glioma (DIPG).

A Computational genomic analysis of patient tissue from diverse childhood brain tumors reveals a spectrum of IL-13Rα2 gene expression levels (benign tumors, n = 14; medulloblastoma, n = 122; ependymoma, n = 60; DIPG, n = 76; hemispheric high-grade glioma (HGG), n = 41). Y-axis shows log2(x + 1) transformed RSEM normalized counts. The normalize Quantiles method was applied and the median log2 relative abundance was calculated for each sample and normalized to a common median of 01,2. Data represent the mean ± SD of individual patient samples. Statistical significance denoted as *: P ≤ 0.05; **: P ≤ 0.01; ****: P ≤ 0.0001; analyzed via one-way ANOVA. B Genomic analysis of patient tissue showing the frequency of IL-13Rα2 alterations based on RNA-Seq mRNA expression data in H3-mutated diffuse midline glioma (DMG)/DIPG, HGG/astrocytoma, and ependymoma. Total number of patient samples: n = 270. Data sourced from the cBio Cancer Genomics Portal (http://cbioportal.org) and the Open Pediatric Brain Tumor Atlas (OpenPBTA) dataset in PedcBioPortal (https://pedcbioportal.org)1,2,3,4,5. C Hematoxylin and eosin (H&E) staining alongside immunohistochemistry (IHC) images from DIPG specimens obtained post-mortem, with higher magnification insets of highlighted tumor regions demonstrating robust IL-13Rα2 staining. Scale bars: 1×: 5000 μm, 20×: 20 μm. (D) GB13 (IL13.E13K-PE4E) shows a potent response in DIPG cell lines compared to non-cancerous cells of the central nervous system. Results are the mean ± SEM of 3 independent dose-response cell viability experiments. ns: P ≥ 0.05; *: P ≤ 0.05; one-way ANOVA. See Supplementary Fig. 1F for full immunoblot of IL-13Rα2 protein data. NHA, normal human astrocytes. E Non-linear least-squares curve fitting illustrating a robust positive correlation between IL-13Rα2 gene expression and GB13 sensitivity, observed across high-grade glioma cell lines, including DIPG. R squared = 0.90.