The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models.
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Date
2019-05-28Author
Martínez-Vélez, N
Garcia-Moure, M
Marigil, M
González-Huarriz, M
Puigdelloses, M
Gallego Pérez-Larraya, J
Zalacaín, M
Marrodán, L
Varela-Guruceaga, M
Laspidea, V
Aristu, JJ
Ramos, LI
Tejada-Solís, S
Díez-Valle, R
Jones, C
Mackay, A
Martínez-Climent, JA
García-Barchino, MJ
Raabe, E
Monje, M
Becher, OJ
Junier, MP
El-Habr, EA
Chneiweiss, H
Aldave, G
Jiang, H
Fueyo, J
Patiño-García, A
Gomez-Manzano, C
Alonso, MM
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Cell Line, Tumor
Animals
Humans
Mice
Adenoviridae
Glioma
Brain Neoplasms
Brain Stem Neoplasms
Disease Models, Animal
Xenograft Model Antitumor Assays
Cell Survival
Computer Simulation
Oncolytic Virotherapy
Oncolytic Viruses
Neoplasm Grading
In Vitro Techniques
Research team
Glioma Team
Language
eng
Date accepted
2019-04-16
License start date
2019-05-28
Citation
Nature communications, 2019, 10 (1), pp. 2235 - ?
Publisher
NATURE PUBLISHING GROUP