%0 Journal Article
%A Garcia-Moure, Marc
%A Gonzalez-Huarriz, Marisol
%A Labiano, Sara
%A Guruceaga, Elizabeth
%A Bandres, Eva
%A Zalacain, Marta
%A Marrodan, Lucia
%A de Andrea, Carlos E
%A Villalba Esparza, María
%A Martínez-Vélez, Naiara
%A Laspidea, Virginia
%A Puigdelloses, Montserrat
%A Gallego Perez-Larraya, Jaime
%A Iñigo-Marco, Ignacio
%A Stripecke, Renata
%A Chan, Jennifer A
%A Raabe, Eric H
%A Kool, Marcel
%A Gomez-Manzano, Candelaria
%A Fueyo, Juan
%A Patiño-García, Ana
%A Alonso, Marta M
%T Delta-24-RGD, an oncolytic adenovirus, increases survival and promotes proinflammatory immune landscape remodeling in models of AT/RT and CNS-PNET.
%J Clinical cancer research
%V 27
%N 6
%@ 1557-3265
%C Philadelphia, Pa. [u.a.]
%I AACR
%M DKFZ-2021-00004
%P 1807-1820
%D 2021
%Z 2021 Mar 15;27(6):1807-1820
%X 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
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33376098
%R 10.1158/1078-0432.CCR-20-3313
%U https://inrepo02.dkfz.de/record/166637