We are thrilled to share our latest work, led by @sara_labiano , on the potential of combining the oncolytic virus Delta-24-RGD with a CD40 agonist to treat diffuse midline gliomas (#DMG). Published in @CellRepMed ! (1/14).🔗

Also, all funding sources @ERC_Research @CienciaGob @gob_na (GRANATE project) @ContraCancerEs #FundaciónADEY @BlancaFundacion @elsuenodevicky @chadtough @criscancer @hqtlvct #CambiandovidasconElsa #másinvestigaciónmásvida (14/14).

We thank our institution @CIMA_unav @ClinicaNavarra @CancerCCUN and all the collaborators who have participated in this work @BecherOren @timphoenixUC @jfueyomargareto @CandelaGManzano and others. (13/14).

Altogether, we propose targeting the tumor myeloid compartment to promote the oncolytic effect of D24-RGD. Our results suggest that enhancing proinflammatory myeloid cells will ensure the generation of strong adaptive anti-DMG immune responses. (12/14).

We next used PLX3397, a CSF1R inhibitor, to deplete microglia and tumor macrophages. Mechanistically, CSF1R inhibition reduced DC recruitment into the tumor and deep cervical lymph nodes. It also decreased key cytokines like CCL5, CXCL9, and CXCL10. (11/14)

To test the functional importance of DCs, we used Batf3KO mice lacking cDC1. The combination therapy lost its survival benefit in these mice, confirming the critical role of cross-presenting DCs in the anti-tumor response. (10/14)

We also saw significant myeloid reprogramming: more DCs, macrophages, and monocytes. DCs in the combo group were highly mature, expressed MHC-II, CD40, and CD86, and produced proinflammatory cytokines. (9/14)

To decipher the mechanism, we analyzed the tumor immune microenvironment 6 days post-treatment. The combination of D24-RGD and anti-CD40 leads to increased CD45 immune cells, CD8 and CD4 T lymphocytes, and regulatory T cells (Tregs). (8/14)

Importantly, mice cured with the combo rejected tumor rechallenge, indicating the induction of long-term anti-tumor immune memory. (7/14)

We locally co-administered D24-RGD and a CD40 agonistic antibody in two orthotopic DMG mouse models (XFM and UC-BL6-C7). The combination significantly improved survival compared to monotherapies and generated long-term responders (40% in XFM). No toxicity was observed. (6/14)

Therefore, we decided to combine the oncolytic and immunomodulating effect of the D24- RGD with targeting APCs through the CD40 receptor to treat DMGs. (5/14).

We have previously demonstrated that the local inoculation of the D24-RGD is safe and increases overall survival in DMG patients. Also, it can modulate the tumor microenvironment, favoring the recruitment of T cells. However, this is insufficient to be curative. (4/14).

Standard-of-care radiotherapy is not curative. It offers symptom relief and slightly extends survival. We urgently need therapies that elicit durable immune responses. (3/14).

#DMG are devastating pediatric brain tumors with very poor prognosis and limited treatment options. Median survival is 9–12 months, and over 90% of patients die within 2 years of diagnosis. (2/14).

Exciting news! We are pleased to share that our PhD student @DanipalalGX has been awarded a prestigious PhD fellowship from @BlancaFundacion to research new oncolytic virotherapy strategies for DMG. Huge congratulations! 🎉👏

It’s been a busy and exciting #pedSNO2025! Amazing to see so much science moving forward to fight pediatric brain tumors. 🎗️.Thanks to the organizers and everyone stopping by to chat! Looking forward to the next one!#NoSurrender.

☢️ Poster 4 – Exploiting conventional type 1 dendritic cells as a new therapeutic strategy.to limit neurocognitive sequelae after pediatric brain tumor radiotherapy. A top-scoring poster from our PhD Student @javiermarco97, co-supervised with @sara_labiano

🐭 Poster 3 – Development of a novel spinal cord diffuse midline glioma model unveils its immune microenvironment and.potential therapeutic strategies. A work by our PhD Student #ReyesHernandez, co-supervised with @sara_labiano and supported by @BlancaFundacion

🧠 Poster 2 – Cognitive and motor effects of TIM-3 blockade in diffuse midline glioma murine models. A work by our PhD Student #SandraMorales

🦠 Poster 1 – Improving oncolytic virotherapy by blocking CD47-SIRPα axis with single-domain antibodies.in diffuse midline gliomas. Presented by @DanipalalGX, co-supervised with #MarcGarciaMoure and supported by @BlancaFundacion