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@ARTICLE{Rechberger:308496,
author = {J. S. Rechberger and W. J. F. Vanbilloen and L. F.
Nonnenbroich$^*$ and J. Ge and R. S. Schrecengost and R. A.
Vaubel and L. Zhang and D. J. Daniels},
title = {{R}adiotherapy plus neoadjuvant and concomitant
{IL}-13{R}α2-directed immunotoxin therapy for diffuse
intrinsic pontine glioma.},
journal = {Communications biology},
volume = {9},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2026-00136},
pages = {78},
year = {2026},
note = {#DKTKZFB26# / 2026 Jan 15;9(1):78},
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.},
cin = {B310 / HD01},
ddc = {570},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41540212},
doi = {10.1038/s42003-025-09155-9},
url = {https://inrepo02.dkfz.de/record/308496},
}