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ONCOINTRABODY SIGNED

Targeting common oncogenes with intracellular monobodies

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 ONCOINTRABODY project word cloud

Explore the words cloud of the ONCOINTRABODY project. It provides you a very rough idea of what is the project "ONCOINTRABODY" about.

kick    intracellular    exist    networks    phosphatases    kinases    penetrating    immunogenicity    tested    cell    stability    antibodies    cells    untargeted    display    domains    binders    innovative    oncoproteins    amino    oncogenesis    inhibition    rapid    limited    nanocarriers    suffers    ed    majority    genes    basic    oncogenic    consequently    molecule    mouse    peptides    potently    remarkable    translation    antibody    central    plasma    largely    tools    class    proteins    drugs    rising    expression    despite    hope    inhibits    interactions    toxins    cancer    patients    mirror    survival    biocompatible    monobody    off    breaking    bacterial    chemical    techniques    suppressor    termed    acids    signalling    alterations    image    kinase    resistance    uses    mediated    therapeutics    tumour    small    previously    oncogenes    endeavour    clinical    ground    monoclonal    medicine    engineered    tumours    sh2    degree    protein    mimics    inhibitors    limit    monobodies    engineering    models    plasticity   

Project "ONCOINTRABODY" data sheet

The following table provides information about the project.

Coordinator
PHILIPPS UNIVERSITAET MARBURG 

Organization address
address: BIEGENSTRASSE 10
city: MARBURG
postcode: 35037
website: www.uni-marburg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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