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 Monje, Oren J. Becher, Marie Pierre Junier, Elias A. El-Habr, Herve Chneiweiss, Guillermo Aldave, Hong Jiang, Juan Fueyo, Ana Patiño-García, Candelaria Gomez-Manzano () and Marta M. Alonso ()
Additional contact information
Naiara Martínez-Vélez: Health Research Institute of Navarra (IDISNA)
Marc Garcia-Moure: Health Research Institute of Navarra (IDISNA)
Miguel Marigil: Health Research Institute of Navarra (IDISNA)
Marisol González-Huarriz: Health Research Institute of Navarra (IDISNA)
Montse Puigdelloses: Health Research Institute of Navarra (IDISNA)
Jaime Gallego Pérez-Larraya: Health Research Institute of Navarra (IDISNA)
Marta Zalacaín: Health Research Institute of Navarra (IDISNA)
Lucía Marrodán: Health Research Institute of Navarra (IDISNA)
Maider Varela-Guruceaga: Health Research Institute of Navarra (IDISNA)
Virginia Laspidea: Health Research Institute of Navarra (IDISNA)
Jose Javier Aristu: Health Research Institute of Navarra (IDISNA)
Luis Isaac Ramos: Health Research Institute of Navarra (IDISNA)
Sonia Tejada-Solís: Health Research Institute of Navarra (IDISNA)
Ricardo Díez-Valle: Health Research Institute of Navarra (IDISNA)
Chris Jones: The Institute of Cancer Research
Alan Mackay: The Institute of Cancer Research
Jose A. Martínez-Climent: Health Research Institute of Navarra (IDISNA)
Maria Jose García-Barchino: Health Research Institute of Navarra (IDISNA)
Eric Raabe: The Johns Hopkins University School of Medicine
Michelle Monje: Stanford University School of Medicine
Oren J. Becher: Northwestern University and Division of Pediatric Hematology-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital
Marie Pierre Junier: Sorbonne Universities
Elias A. El-Habr: Sorbonne Universities
Herve Chneiweiss: Sorbonne Universities
Guillermo Aldave: Texas Children’s Hospital, Baylor College of Medicine
Hong Jiang: The University of Texas MD Anderson Cancer Center
Juan Fueyo: The University of Texas MD Anderson Cancer Center
Ana Patiño-García: Health Research Institute of Navarra (IDISNA)
Candelaria Gomez-Manzano: The University of Texas MD Anderson Cancer Center
Marta M. Alonso: Health Research Institute of Navarra (IDISNA)

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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).

Date: 2019
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DOI: 10.1038/s41467-019-10043-0

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