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Development of an immune-armed therapeutic adenoviral platform for pediatric brain tumors

Project description

Oncolytic virus therapy for aggressive paediatric brain tumours

Oncolytic viruses are engineered to selectively infect and kill cancer cells while triggering an immune response against the tumour. They have emerged as a promising cancer treatment. The ERC-funded POPCORN project aims to develop a next-generation oncolytic virus therapy for diffuse midline glioma, one of the most malignant paediatric brain tumours with a median survival of less than 14 months. Researchers propose the engineering of oncolytic adenoviruses that deliver immunomodulatory single-domain antibodies directly to the tumour. By augmenting the immunostimulating function of oncolytic viruses, the study has the potential to provide a revolutionary treatment for difficult-to-treat childhood brain tumours.

Objective

Diffuse Midline Gliomas (DMGs) are the most aggressive pediatric brain tumors in desperate need of curative treatment. The median life expectancy of these children remains below 14 months after diagnosis, and nearly none survive beyond the second year. Similarly, for other high-risk pediatric brain tumors, there is hardly any option after recurrence, and long-term survivors are faced with life-long sequelae that impact their quality of life. In this scenario, there is an urgent need for innovative, efficacious, and safe therapies for these patients. Oncolytic viruses are promising anticancer biotherapeutic agents that offer a unique combination of safety profile, direct antineoplastic activity, and the induction of anti-tumor immune responses. Recently, a Phase I clinical trial showed that combining the oncolytic adenovirus Delta-24-RGD and radiotherapy is non-toxic and results in anti-tumor responses and prolonged median overall survival (17.8 months) in patients. However, results are still insufficient to be curative due to counteracting mechanisms intrinsic to the tumor microenvironment and also triggered by the virus that eventually exceeds its immunostimulatory properties. The proposed technology, termed “POPCORN”', is an oncolytic-based platform capable of expressing immunomodulatory single-domain antibodies directed to intrinsic targets in these tumors. We will develop the POPCORN Proof of Concept using a state-of-the-art experimental approach and validate its safety and efficacy in vitro and relevant in vivo DMG models. We will also perform IND-enabling studies and apply for PUMA/PRIME designation. Additionally, we will work on the IPR strategy, and a value proposition to develop and commercialize the POPCORN platform will be generated. We envision the POPCORN platform becoming a game changer in treating DMGs, providing a one-of-a-kind tool for eliminating these aggressive tumors that could be extensive to other difficult-to-treat pediatric brain tumors.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

UNIVERSIDAD DE NAVARRA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
CAMPUS UNIVERSITARIO EDIFICIO CENTRAL
31080 PAMPLONA
Spain

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Region
Noreste Comunidad Foral de Navarra Navarra
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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