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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.

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

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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