ONCOINTRABODY SIGNED
Targeting common oncogenes with intracellular monobodies
Total Cost €
0EC-Contrib. €
0Partnership
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Project "ONCOINTRABODY" data sheet
The following table provides information about the project.
| Coordinator |
PHILIPPS UNIVERSITAET MARBURG
Organization address contact info |
| Coordinator Country | Germany [DE] |
| Total cost | 1˙996˙055 € |
| EC max contribution | 1˙996˙055 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-08-01 to 2023-03-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | PHILIPPS UNIVERSITAET MARBURG | DE (MARBURG) | coordinator | 1˙419˙148.00 |
| 2 | ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE | CH (LAUSANNE) | participant | 576˙906.00 |
Map
Project objective
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.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2020 |
Oliver Hantschel, Matthew Biancalana, Shohei Koide Monobodies as enabling tools for structural and mechanistic biology published pages: 167-174, ISSN: 0959-440X, DOI: 10.1016/j.sbi.2020.01.015 |
Current Opinion in Structural Biology 60 | 2020-04-07 |
| 2019 |
Nadine Eliane Schmit, Katyayanee Neopane, Oliver Hantschel Targeted Protein Degradation through Cytosolic Delivery of Monobody Binders Using Bacterial Toxins published pages: 916-924, ISSN: 1554-8929, DOI: 10.1021/acschembio.9b00113 |
ACS Chemical Biology 14/5 | 2020-04-07 |
| 2017 |
Hantschel, Oliver Monobodies as possible next-generation protein therapeutics – a perspective published pages: , ISSN: 1424-7860, DOI: 10.4414/smw.2017.14545 |
Swiss Medical Weekly 147/4748 | 2020-03-03 |
| 2017 |
Sina Reckel, Charlotte Gehin, Delphine Tardivon, Sandrine Georgeon, Tim Kükenshöner, Frank Löhr, Akiko Koide, Lena Buchner, Alejandro Panjkovich, Aline Reynaud, Sara Pinho, Barbara Gerig, Dmitri Svergun, Florence Pojer, Peter Güntert, Volker Dötsch, Shohei Koide, Anne-Claude Gavin, Oliver Hantschel Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02313-6 |
Nature Communications 8/1 | 2020-03-03 |
| 2017 |
Tim Kükenshöner, Nadine Eliane Schmit, Emilie Bouda, Fern Sha, Florence Pojer, Akiko Koide, Markus Seeliger, Shohei Koide, Oliver Hantschel Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies published pages: 1364-1380, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2017.03.023 |
Journal of Molecular Biology 429/9 | 2020-03-03 |
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