Journal Article

DKFZ-2026-00136

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiotherapy plus neoadjuvant and concomitant IL-13Rα2-directed immunotoxin therapy for diffuse intrinsic pontine glioma.

Rechberger, J. S. ; Vanbilloen, W. J. F. ; Nonnenbroich, L. F.DKFZ* ; Ge, J. ; Schrecengost, R. S. ; Vaubel, R. A. ; Zhang, L. ; Daniels, D. J.

2026
Springer Nature London

Abstract: Radiotherapy (RT) is the standard-of-care for diffuse intrinsic pontine glioma (DIPG); however, it functions as a palliative treatment. Interleukin 13 receptor subunit alpha 2 (IL-13Rα2) is upregulated in most DIPG tumors, posing a promising therapeutic target. Immunotherapies harnessing IL-13Rα2 to selectively deliver cytotoxic payloads such as pseudomonas exotoxin A (PE) are safe in DIPG patients and efficacious in preclinical disease models. Here, we used DIPG cell lines and mouse models to compare RT alone with RT plus the IL-13Rα2-targeted PE immunotoxin GB13 (IL13.E13K-PE4E). DNA strand breaks were evaluated by γH2AX and apoptosis, as well as other on-target effects, by Western blot and immunofluorescence. Cell viability and colony formation assays delineated cell viability and proliferation. In vivo efficacy was based on survival of mice with orthotopic tumors. Animals received fractionated focal irradiation and neoadjuvant and concomitant GB13 by convection-enhanced delivery. GB13 improved the efficacy of RT in vitro through inhibition of DNA damage repair and convergent modulation of apoptotic signaling. Combined RT and intratumoral administration of GB13 decreased tumor burden and prolonged survival in orthotopic xenograft and genetically engineered mouse models. These findings indicate that RT plus GB13 is well tolerated and effective, informing future investigation of a novel therapeutic approach for DIPG.

Note: #DKTKZFB26# / 2026 Jan 15;9(1):78

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Contributing Institute(s):

1. KKE Pädiatrische Onkologie (B310)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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