Abstract

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).

The oncolytic virus Delta-24-RGD is in clinical trial for adult glioma. Here, the authors show that this virus elicits an immune response in mouse models of pediatric high-grade glioma and diffuse pontine intrinsic glioma, resulting in improved survival.

Details

Title
The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models
Author
Martínez-Vélez Naiara 1 ; Garcia-Moure, Marc 2 ; Marigil Miguel 2 ; González-Huarriz Marisol 2 ; Puigdelloses Montse 3 ; Gallego Pérez-Larraya Jaime 3   VIAFID ORCID Logo  ; Zalacaín Marta 2 ; Marrodán Lucía 2 ; Varela-Guruceaga Maider 2 ; Laspidea Virginia 2 ; Aristu Jose Javier 4 ; Ramos, Luis Isaac 4 ; Tejada-Solís, Sonia 5 ; Díez-Valle, Ricardo 5 ; Jones, Chris 6 ; Mackay, Alan 6 ; Martínez-Climent, Jose A 7 ; García-Barchino, Maria Jose 8 ; Raabe, Eric 9   VIAFID ORCID Logo  ; Monje, Michelle 10   VIAFID ORCID Logo  ; Becher, Oren J 11 ; Junier Marie Pierre 12 ; El-Habr, Elias A 12 ; Chneiweiss Herve 12   VIAFID ORCID Logo  ; Aldave Guillermo 13 ; Jiang, Hong 14   VIAFID ORCID Logo  ; Fueyo, Juan 15 ; Patiño-García, Ana 16   VIAFID ORCID Logo  ; Gomez-Manzano Candelaria 14 ; Alonso, Marta M 16   VIAFID ORCID Logo 

1  Health Research Institute of Navarra (IDISNA), Pamplona, Spain; University of Navarra, Program of Solid Tumors, Center for the Applied Medical Research (CIMA), Navarra, Spain (GRID:grid.5924.a) (ISNI:0000000419370271); Clínica Universidad de Navarra, Department of Pediatrics, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
2  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.411730.0); University of Navarra, Program of Solid Tumors, Center for the Applied Medical Research (CIMA), Navarra, Spain (GRID:grid.5924.a) (ISNI:0000000419370271); Clínica Universidad de Navarra, Department of Pediatrics, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
3  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.411730.0); University of Navarra, Program of Solid Tumors, Center for the Applied Medical Research (CIMA), Navarra, Spain (GRID:grid.5924.a) (ISNI:0000000419370271); Clínica Universidad de Navarra, Department of Neurology, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
4  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.411730.0); Clínica Universidad de Navarra, Department of Radiation Oncology, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
5  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.411730.0); Clínica Universidad de Navarra, Department of Neurosurgery, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
6  The Institute of Cancer Research, Division of Molecular Pathology, Surrey, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623); The Institute of Cancer Research, Division of Cancer Therapeutics, Surrey, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
7  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.18886.3f); University of Navarra, CIBERONC, Pamplona, Division of Hematopoietic Tumors, Center for the Applied Medical Research (CIMA), Pamplona, Spain (GRID:grid.5924.a) (ISNI:0000000419370271) 
8  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.5924.a); University of Navarra, CIBERONC, Pamplona, Division of Hematopoietic Tumors, Center for the Applied Medical Research (CIMA), Pamplona, Spain (GRID:grid.5924.a) (ISNI:0000000419370271) 
9  The Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); The Johns Hopkins University School of Medicine, Division of Pediatric Oncology, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
10  Stanford University School of Medicine, Department of Neurology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
11  Northwestern University and Division of Pediatric Hematology-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital, Department of Pediatrics, Chicago, USA (GRID:grid.413808.6) (ISNI:0000 0004 0388 2248) 
12  Sorbonne Universities, CNRS UMR8246, Inserm U1130, Neuroscience Paris Seine - IBPS, Paris, France (GRID:grid.462844.8) (ISNI:0000 0001 2308 1657) 
13  Texas Children’s Hospital, Baylor College of Medicine, Division of Pediatric Neurosurgery, Department of Surgery, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
14  The University of Texas MD Anderson Cancer Center, Department of NeuroOncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
15  The University of Texas MD Anderson Cancer Center, Department of NeuroOncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Neurosurgery, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
16  Health Research Institute of Navarra (IDISNA), Pamplona, Spain (GRID:grid.240145.6); University of Navarra, Program of Solid Tumors, Center for the Applied Medical Research (CIMA), Navarra, Spain (GRID:grid.5924.a) (ISNI:0000000419370271); Clínica Universidad de Navarra, Department of Pediatrics, Pamplona, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10043-0
ProQuest document ID
2231412473
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.