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dc.contributor.author
Schmid, Anja Sophie
dc.contributor.author
Neri, Dario
dc.date.accessioned
2019-09-30T08:10:56Z
dc.date.available
2019-09-28T08:10:42Z
dc.date.available
2019-09-30T08:10:56Z
dc.date.issued
2019-07-26
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0219313
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/367051
dc.identifier.doi
10.3929/ethz-b-000367051
dc.description.abstract
Interleukin-15 (IL15) is one of the most important cytokines currently being considered for cancer therapy applications. It is thought that by administering IL15 in complex with its cognate receptor alpha chain (IL15Rα) its biological activity could be increased manifold. We produced a fusion protein of mouse IL15Rα and the F8 antibody, that targets the alternatively-spliced extra-domain A (EDA) of fibronectin, which is overexpressed in many types of cancer. The fusion protein F8IL15Rα was cloned, expressed and characterized in vitro and its ability to bind to mouse IL15 was assessed with both size exclusion chromatography (SEC) and surface plasmon resonance (SPR) experiments. Furthermore, mouse and human IL15 and their corresponding Fc fused IL15Rα subunits were purchased, characterized and used to compare the capacity of F8IL15Rα to generate complexes. Surprisingly, none of the IL15Rα fusion proteins showed IL15 complexation on SEC. However, on SPR, F8IL15Rα displayed the ability to bind IL15. In a cell-based activity assay none of the IL15Rα fusions were able to increase cellular proliferation in combination with IL15 compared to IL15 alone. A better understanding of the molecular requirements for effective IL15 signalling are likely to be important for the development of IL15-based biopharmaceuticals.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLoS
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Design and characterisation of a novel interleukin-15 receptor alpha fusion protein and analysis of interleukin-15 complexation
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS ONE
ethz.journal.volume
14
en_US
ethz.journal.issue
7
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0219313
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature
en_US
ethz.identifier.wos
ethz.publication.place
San Francisco, CA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03463 - Neri, Dario (ehemalig) / Neri, Dario (former)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03463 - Neri, Dario (ehemalig) / Neri, Dario (former)
ethz.grant.agreementno
163479
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Exzellenzbeitrag in Biologie und Medizin (Abteilung III)
ethz.date.deposited
2019-09-28T08:10:47Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-09-30T08:11:38Z
ethz.rosetta.lastUpdated
2021-02-15T06:03:51Z
ethz.rosetta.versionExported
true
ethz.COinS
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