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CORDIS - Résultats de la recherche de l’UE
CORDIS

Next generation ketoamide inhibitors of fibroblast activation protein (FAP) to revolutionize radionuclide therapy in cancer.

Objectif

Fibroblast activation protein (FAP) is a serine protease that is highly expressed on cancer-associated-fibroblasts (CAFs), in nearly all tumor types. Its limited presence in healthy tissues makes it an attractive diagnostic and therapeutic biomarker for cancer. UAMC1110, a potent and specific FAP inhibitor discovered by the host, opened the way for the development of the so-called ‘FAPIs’. These are tumor-targeting molecules composed of a UAMC1110 moiety and a radionuclide. The latter can either be a diagnostic radionuclide for PET imaging, or a more cytotoxic radionuclide for cancer therapy. Radiodiagnostic FAPIs are now entering clinical practice, but their therapeutic counterparts face challenges, related to the relatively short tumor residence time of currently available molecules. The latter leads to significant ‘leaking’ of toxic radioactivity from the tumor. To overcome this issue, we will develop ‘ketoFAPIs’ that form long-lived covalent bonds with FAP. This should already ensure significantly longer tumor residence. The ketoFAPIs will also be bound to the surface of gold nanoparticles (AuNPs). The resulting constructs could have further increased tumor residence through the ‘multivalency’ effect. This interdisciplinary proposal covers 1) the chemical preparation of novel ketoFAPIs and derived AuNPs, 2) their in vitro characterization and 3) in vivo investigation in a mouse model of colorectal cancer. Overall, the project can lead to safer and more efficient FAPIs for radiotherapy applications. The status of FAP as a ‘pan-cancer’ biomarker entails that these FAPIs could be applied in nearly all cancer types.

Champ scientifique (EuroSciVoc)

Mots‑clés

Programme(s)

Thème(s)

Régime de financement

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Appel à propositions

(s’ouvre dans une nouvelle fenêtre) HORIZON-MSCA-2023-PF-01

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Coordinateur

UNIVERSITEIT ANTWERPEN
Contribution nette de l'UE
€ 191 760,00
Adresse
PRINSSTRAAT 13
2000 Antwerpen
Belgique
Région
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée