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@ARTICLE{GarciaMoure:166637,
author = {M. Garcia-Moure and M. Gonzalez-Huarriz and S. Labiano and
E. Guruceaga and E. Bandres and M. Zalacain and L. Marrodan
and C. E. de Andrea and M. Villalba Esparza and N.
Martínez-Vélez and V. Laspidea and M. Puigdelloses and J.
Gallego Perez-Larraya and I. Iñigo-Marco and R. Stripecke
and J. A. Chan and E. H. Raabe and M. Kool$^*$ and C.
Gomez-Manzano and J. Fueyo and A. Patiño-García and M. M.
Alonso},
title = {{D}elta-24-{RGD}, an oncolytic adenovirus, increases
survival and promotes proinflammatory immune landscape
remodeling in models of {AT}/{RT} and {CNS}-{PNET}.},
journal = {Clinical cancer research},
volume = {27},
number = {6},
issn = {1557-3265},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2021-00004},
pages = {1807-1820},
year = {2021},
note = {2021 Mar 15;27(6):1807-1820},
abstract = {Atypical teratoid/rhabdoid tumors (AT/RTs) and primitive
neuroectodermal tumors (CNS-PNETs) are pediatric brain
tumors with poor survival and life-long negative side
effects. Here, the aim was to characterize the efficacy and
safety of the oncolytic adenovirus Delta-24-RGDs, which
selectively replicates in and kills tumor cells.Delta-24-RGD
determinants for infection and replication were evaluated in
patient expression data sets. Viral replication and
cytotoxicity were assessed invitro in a battery of CNS-PNET
and AT/RT cell lines. In vivo, efficacy was determined in
different orthotopic mouse models, including early and
established tumor models, a disseminated AT/RT lesion model
and immunocompetent humanized mouse models
(hCD34+-NSG-SGM3).Delta-24-RGD infected and replicated
efficiently in all the cell lines tested. In addition, the
virus induced dose-dependent cytotoxicity (IC50 below 1
PFU/cell) and the release of immunogenic markers. Invivo, a
single intratumoral Delta-24-RGD injection (107 or 108 PFU)
significantly increased survival and led to long-term
survival in AT/RT and PNET models. Delta-24-RGD hindered the
dissemination of AT/RTs and increased survival, leading to
$70\%$ of long-term survivors. Of relevance, viral
administration to established tumor masses (30 days after
engraftment) showed therapeutic benefit. In humanized
immunocompetent models, Delta-24-RGD significantly extended
the survival of mice bearing AT/RTs or PNETs (ranging from
11 to 27 days) and did not display any toxicity associated
with inflammation. Immunophenotyping of Delta-24-RGD-treated
tumors revealed increased CD8+ T cell
infiltration.Delta-24-RGD is a feasible therapeutic option
for AT/RTs and CNS-PNETs. This work constitutes the basis
for potential translation to the clinical setting.},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33376098},
doi = {10.1158/1078-0432.CCR-20-3313},
url = {https://inrepo02.dkfz.de/record/166637},
}