Scientific publications 

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

Martínez-Vélez N (1,2,3), Garcia-Moure M (1,2,3), Marigil M (1,2,3), González-Huarriz M (1,2,3), Puigdelloses M (1,2,4), Gallego Pérez-Larraya J (1,2,4), Zalacaín M (1,2,3), Marrodán L (1,2,3), Varela-Guruceaga M (1,2,3), Laspidea V (1,2,3), Aristu JJ (1,5), Ramos LI (1,5), Tejada-Solís S (1,6), Díez-Valle R (1,6), Jones C (7,8), Mackay A (7,8), Martínez-Climent JA (1,9), García-Barchino MJ (1,9), Raabe E (10,11), Monje M (12), Becher OJ (13), Junier MP (14), El-Habr EA (14), Chneiweiss H (14), Aldave G (15), Jiang H (16), Fueyo J (16,17), Patiño-García A (1,2,3), Gomez-Manzano C (18), Alonso MM (19,20,21).

(1) Health Research Institute of Navarra (IDISNA), Pamplona, Navarra, Spain.
(2) Program of Solid Tumors, Center for the Applied Medical Research (CIMA), University of Navarra, Navarra, Pamplona, Spain.
(3) Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.
(4) Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.
(5) Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
(6) Department of Neurosurgery, Clínica Universidad de Navarra, Pamplona, Spain.
(7) Division of Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey, SM2 5NG, UK.
(8) Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, Surrey, SM2 5NG, UK.
(9) Division of Hematopoietic Tumors, Center for the Applied Medical Research (CIMA), University of Navarra, CIBERONC, Pamplona, Pamplona, Navarra, Spain.
(10) Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
(11) Division of Pediatric Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
(12) Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
(13) Department of Pediatrics, Northwestern University and Division of Pediatric Hematology-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, USA.
(14) CNRS UMR8246, Inserm U1130, Neuroscience Paris Seine - IBPS, Sorbonne Universities, Paris, France.
(15) Division of Pediatric Neurosurgery, Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
(16) Department of NeuroOncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
(17) Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
(18) Department of NeuroOncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
(19) Health Research Institute of Navarra (IDISNA), Pamplona, Navarra, Spain.
(20) Program of Solid Tumors, Center for the Applied Medical Research (CIMA), University of Navarra, Navarra, Pamplona, Spain.
(21) Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.

Magazine: Nature Communications

Date: May 28, 2019

Neurology [SP] Radiation Oncology Brain Tumour Area Neurosurgery Department Pediatría [SP]

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.

CITATION  Nat Commun. 2019 May 28;10(1):2235. doi: 10.1038/s41467-019-10043-0

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