TY - JOUR
AU - Garcia-Moure, Marc
AU - Gonzalez-Huarriz, Marisol
AU - Labiano, Sara
AU - Guruceaga, Elizabeth
AU - Bandres, Eva
AU - Zalacain, Marta
AU - Marrodan, Lucia
AU - de Andrea, Carlos E
AU - Villalba Esparza, María
AU - Martínez-Vélez, Naiara
AU - Laspidea, Virginia
AU - Puigdelloses, Montserrat
AU - Gallego Perez-Larraya, Jaime
AU - Iñigo-Marco, Ignacio
AU - Stripecke, Renata
AU - Chan, Jennifer A
AU - Raabe, Eric H
AU - Kool, Marcel
AU - Gomez-Manzano, Candelaria
AU - Fueyo, Juan
AU - Patiño-García, Ana
AU - Alonso, Marta M
TI - Delta-24-RGD, an oncolytic adenovirus, increases survival and promotes proinflammatory immune landscape remodeling in models of AT/RT and CNS-PNET.
JO - Clinical cancer research
VL - 27
IS - 6
SN - 1557-3265
CY - Philadelphia, Pa. [u.a.]
PB - AACR
M1 - DKFZ-2021-00004
SP - 1807-1820
PY - 2021
N1 - 2021 Mar 15;27(6):1807-1820
AB - 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
LB - PUB:(DE-HGF)16
C6 - pmid:33376098
DO - DOI:10.1158/1078-0432.CCR-20-3313
UR - https://inrepo02.dkfz.de/record/166637
ER -