Next generation ketoamide inhibitors of fibroblast activation protein FAP to r...
Next generation ketoamide inhibitors of fibroblast activation protein FAP to revolutionize radionuclide therapy in cancer.
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 th...
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31/10/2026
UANTWERPEN
192K€
Presupuesto del proyecto: 192K€
Líder del proyecto
UNIVERSITEIT ANTWERPEN
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Fecha límite participación
Sin fecha límite de participación.
Financiación
concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto
el día 2024-10-01
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Información proyecto KetoFAPIs
Duración del proyecto: 24 meses
Fecha Inicio: 2024-10-01
Fecha Fin: 2026-10-31
Líder del proyecto
UNIVERSITEIT ANTWERPEN
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
192K€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
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.