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Validation of artificial intelligence-based minibinders and inhibitors of Midkine in immune resistant tumours

Ziel

This proposal aims to validate artificial intelligence (AI)-designed minibinders and blockers of the growth factor Midkine (MDK) as anticancer agents to bypass resistance to current immunotherapies. The rationale stems from reports by our laboratory in Nature, Nature Medicine, EMBO Mol Reports and Nature Cancer describing pro-metastatic and immunosuppressive functions of MDK in melanoma, the most aggressive form of skin cancer. In particular, our work identified MDK as a driver of the “hot-into-cold” switch that underlies immune evasion and resistance to immune checkpoint blockade. We have also described immunomodulatory roles of MDK in gliomas, lung adenocarcinomas and kidney renal carcinomas, among others. These data are backed by an increasing number of independent studies reporting a broad spectrum of protumorigenic functions of MDK in diverse hematological and solid cancers. Indeed, MDK has been actively pursued as a ther This proposal focuses on the characterization and preclinical validation of artificial intelligence (AI)-designed minibinders that target Midkine (MDK), a protein that is overexpressed in multiple cancers, including melanoma. We have previously demonstrated that MDK plays a critical role in metastasis, immune suppression, and resistance to immune checkpoint inhibitors (ICIs), with analyses of preclininical drug testing backed by publications in Nature and Nature Medicine. We have identified 40 mini-binders and selected a subset with different structural features for further validation. These mini-binders will be validated in preclinical models to assess their potential as new therapeutics for MDK-driven cancers. The project aims to provide a novel therapeutic strategy to restore immune competency in immune-resistant tumors, particularly melanoma, with broader applications for other cancers. The proposal involves also a patentability study and analysis of market assessment for potential development of the intellectual property to be generated.

Wissenschaftliches Gebiet (EuroSciVoc)

Programm/Programme

Thema/Themen

Finanzierungsplan

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

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Aufforderung zur Vorschlagseinreichung

(öffnet in neuem Fenster) ERC-2026-POC

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Gastgebende Einrichtung

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III
Netto-EU-Beitrag
€ 150 000,00
Adresse
C MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spanien
Region
Comunidad de Madrid Comunidad de Madrid Madrid
Aktivitätstyp
Research Organisations
Links
Gesamtkosten
Keine Daten

Begünstigte (1)