Innovating Works

ONCOINTRABODY

Financiado
Targeting common oncogenes with intracellular monobodies
Oncogenic signalling networks display a remarkable degree of plasticity. Despite only a limited number of alterations in oncogenes and tumour suppressor genes in most tumours, the majority of targeted therapeutics (monoclonal anti... Oncogenic signalling networks display a remarkable degree of plasticity. Despite only a limited number of alterations in oncogenes and tumour suppressor genes in most tumours, the majority of targeted therapeutics (monoclonal antibodies and small-molecule kinase inhibitors) does not strongly improve the survival of cancer patients and suffers from the rapid development of resistance. The rising number of targeted drugs in clinical use inhibits only a very limited number of protein targets (largely kinases). Consequently, most intracellular non-kinase oncoproteins remain untargeted. We have previously established the use of small engineered antibody mimics, termed monobodies, to potently and specifically target intracellular protein-protein interactions mediated by the SH2 domains of oncogenic kinases and phosphatases. Expression of SH2-targeting monobodies resulted in the inhibition of signalling and oncogenesis of these oncoproteins. Here, we aim at developing monobody binders to 10 key intracellular oncoproteins for which no chemical inhibitors exist and testing their activity in cancer cells. To enable a possible clinical translation of monobody-based therapeutics, we will develop methods to deliver monobody proteins into cells, including cell-penetrating peptides, bacterial toxins and biocompatible nanocarriers. 'Mirror-image' monobodies, composed of D-amino acids, will be developed and tested to increase intracellular and plasma stability and to limit immunogenicity. The developed monobodies and delivery systems are planned to be tested in mouse cancer models. Our goal is to establish monobodies as novel class of intracellular protein-based therapeutics. We hope to kick off their use beyond basic research tools towards possible applications in cancer patients. This innovative endeavour uses state-of-the-art protein engineering techniques to address a central problem in cancer medicine and may provide a ground-breaking new approach to target cancer. ver más
31/12/2023
UMR
2M€
Duración del proyecto: 92 meses Fecha Inicio: 2016-04-18
Fecha Fin: 2023-12-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2023-12-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2015: ERC Consolidator Grant
Cerrada hace 9 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
PHILIPPS UNIVERSITAET MARBURG No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5