The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Naiara Martínez-Vélez, Marc Garcia-Moure, Miguel Marigil, Marisol González-Huarriz, Montse Puigdelloses, Jaime Gallego Pérez-Larraya, Marta Zalacaín, Lucía Marrodán, Maider Varela-Guruceaga, Virginia Laspidea, Jose Javier Aristu, Luis Isaac Ramos, Sonia Tejada-Solís, Ricardo Díez-Valle, Chris Jones, Alan Mackay, Jose A. Martínez-Climent, Maria Jose García-Barchino, Eric Raabe, Michelle MonjeOren J. Becher, Marie Pierre Junier, Elias A. El-Habr, Herve Chneiweiss, Guillermo Aldave, Hong Jiang, Juan Fueyo, Ana Patiño-García, Candelaria Gomez-Manzano, Marta M. Alonso

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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).

Original languageEnglish (US)
Article number2235
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - May 28 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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, J. J., Ramos, L. I., Tejada-Solís, S., Díez-Valle, R., Jones, C., Mackay, A., Martínez-Climent, J. A., García-Barchino, M. J., Raabe, E., ... Alonso, M. M. (2019). The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Nature communications, 10(1), [2235]. https://doi.org/10.1038/s41467-019-10043-0