Home > Publications database > Delta-24-RGD, an oncolytic adenovirus, increases survival and promotes proinflammatory immune landscape remodeling in models of AT/RT and CNS-PNET. > print

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024 7 _ |a 10.1158/1078-0432.CCR-20-3313
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024 7 _ |a 1078-0432
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024 7 _ |a 1557-3265
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037 _ _ |a DKFZ-2021-00004
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Garcia-Moure, Marc
|0 0000-0002-4365-7753
|b 0
245 _ _ |a Delta-24-RGD, an oncolytic adenovirus, increases survival and promotes proinflammatory immune landscape remodeling in models of AT/RT and CNS-PNET.
260 _ _ |a Philadelphia, Pa. [u.a.]
|c 2021
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336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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500 _ _ |a 2021 Mar 15;27(6):1807-1820
520 _ _ |a 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.
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700 1 _ |a Gonzalez-Huarriz, Marisol
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700 1 _ |a Labiano, Sara
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700 1 _ |a Guruceaga, Elizabeth
|0 0000-0003-0547-681X
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700 1 _ |a Bandres, Eva
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700 1 _ |a Zalacain, Marta
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700 1 _ |a Marrodan, Lucia
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700 1 _ |a de Andrea, Carlos E
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700 1 _ |a Villalba Esparza, María
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700 1 _ |a Martínez-Vélez, Naiara
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700 1 _ |a Laspidea, Virginia
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700 1 _ |a Puigdelloses, Montserrat
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700 1 _ |a Gallego Perez-Larraya, Jaime
|0 0000-0003-2969-0116
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700 1 _ |a Iñigo-Marco, Ignacio
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700 1 _ |a Stripecke, Renata
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700 1 _ |a Chan, Jennifer A
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700 1 _ |a Raabe, Eric H
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700 1 _ |a Kool, Marcel
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700 1 _ |a Gomez-Manzano, Candelaria
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700 1 _ |a Fueyo, Juan
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700 1 _ |a Patiño-García, Ana
|0 0000-0002-4066-8203
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700 1 _ |a Alonso, Marta M
|0 0000-0002-7520-7351
|b 21
773 _ _ |a 10.1158/1078-0432.CCR-20-3313
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