TY - JOUR
T1 - The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models
AU - Martínez-Vélez, Naiara
AU - Garcia-Moure, Marc
AU - Marigil, Miguel
AU - González-Huarriz, Marisol
AU - Puigdelloses, Montse
AU - Gallego Pérez-Larraya, Jaime
AU - Zalacaín, Marta
AU - Marrodán, Lucía
AU - Varela-Guruceaga, Maider
AU - Laspidea, Virginia
AU - Aristu, Jose Javier
AU - Ramos, Luis Isaac
AU - Tejada-Solís, Sonia
AU - Díez-Valle, Ricardo
AU - Jones, Chris
AU - Mackay, Alan
AU - Martínez-Climent, Jose A.
AU - García-Barchino, Maria Jose
AU - Raabe, Eric
AU - Monje, Michelle
AU - Becher, Oren J.
AU - Junier, Marie Pierre
AU - El-Habr, Elias A.
AU - Chneiweiss, Herve
AU - Aldave, Guillermo
AU - Jiang, Hong
AU - Fueyo, Juan
AU - Patiño-García, Ana
AU - Gomez-Manzano, Candelaria
AU - Alonso, Marta M.
N1 - Funding Information:
We are very grateful to Dr. Laura Guembe and the imaging core for the help with all the immunohistochemistry. This work was supported by the European Union (Marie Curie IRG270459; to M.M. Alonso), the Instituto de Salud Carlos III y los Fondos Feder Europeos (PI13/125; PI16/0066 to M.M. Alonso), the Spanish Ministry of Science and Innovation (Ramón y Cajal contract RYC-2009–05571, IEDI-2015-00638, and BIO2015-68990-REDT to M.M. Alonso), the Department of Health of the Government of Navarra (to M.M. Alonso), the Basque Foundation for Health Research (BIOEF, BIO13/CI/005), Foundation LA CAIXA/Caja Navarra (A-PG, MMA), Foundation “El sueño de Vicky”, Asociation Pablo Ugarte-Fuerza Julen (A-PG,MMA), and DOD team science award (MMA, JF, and CG-M). The Cancer Prevention and Research Institute of Texas (RP170066; C-GM and JF, the Rory David Deutsch Foundation (OJB) and Instituto de Salud Carlos III—CIBERONC (to JAM-C and MJG-B). This project has received funding from the European Research Council (ERC) under the European Union´s Horizon 2020 research and innovation programme (grant agreement No. 817884; ViroPedTher).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/5/28
Y1 - 2019/5/28
N2 - Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).
AB - Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).
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U2 - 10.1038/s41467-019-10043-0
DO - 10.1038/s41467-019-10043-0
M3 - Article
C2 - 31138805
AN - SCOPUS:85066314046
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2235
ER -