Pediatric Oncology Seminar Series (PACE Series) - U1330

**Marta Maria Alonso Roldan**, Co-director of the program on solid tumors, Principal investigator, Advanced Therapies Group for Pediatric Solid Tumors
*Public University of Navarre*

Pediatric Oncology Seminar Series (PACE Series) – U1330

« Oncolytic virotherapy for aggressive pediatric brain tumor»

Monday, March 2nd 2026 at 11:30AM
Join on-site : Centre de recherche – Paris Amphithéâtre Hélène Martel Massignac

Oncolytic adenoviruses offer a powerful strategy to exploit the biological vulnerabilities of pediatric high-grade brain tumors, including diffuse midline gliomas (DMGs).

We engineer Delta-24–based adenoviruses to couple direct oncolysis with spatially restricted immune activation while preserving safety in the developing brain. Using orthotopic models in clinically relevant CNS locations, we showed that Delta-24-RGD and its clinical counterpart DNX-2401 induce robust antitumor and immune responses and synergize with radiotherapy and agents such as ONC201. To overcome the profoundly immunosuppressive DMG microenvironment, we developed armed vectors, such as Delta-24-ACT, that provide in situ 4-1BB-mediated costimulation. Mechanistic studies identified TIM-3 as a key regulator of the tumor–immune interface, and its blockade, via antibodies or RNA aptamers, enhances tumor control and durable immune memory. Ongoing work using nanobodies and aptamer-armed viruses aims to refine localized immunomodulation and rationally integrate virotherapy with next-generation immunotherapies for pediatric brain tumors.

Selected publications

1. Targeting the CD40 Co-stimulatory Receptor to Improve Virotherapy Efficacy in Diffuse Midline Gliomas. Labiano S, […] Alonso MM*(24/24 CA). Q1, Cell Rep Med Q1. 2025 accepted (may 8^th).

2. Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models. Ausejo-Mauleon I, […] Alonso MM*(14/14 CA). Q1, JCI Insight. 2024;9(18):e175257. doi: 10.1172/jci.insight.175257.

3.The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models. de la Nava D, […] Alonso MM* (32/32 CA). Q1 Neuro Oncol. 2024:noae066. doi:10.1093/neuonc/noae066.

4. TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory.Ausejo-Mauleon I, […] and Alonso MM* (35/35 CA). Q1 Cancer Cell 202341(11):1911-1926.e8.doi: 10.1016/j.ccell.2023.09.001.

5. Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. Gállego Pérez-Larraya J, […] Alonso MM*. (30/30 CA) Q1 N Engl J Med. 2022 386(26):2471-2481. doi: 10.1056/NEJMoa2202028.

Editorial: Virotherapy for Brain Tumors – Defining the Path to Success. Galanis E. N Engl J Med. 2022 Jun 30;386(26):2520-2522. doi: 10.1056/NEJMe2205032.