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dc.contributor.author
Gouyou, Baptiste
dc.contributor.author
Ongaro, Tiziano
dc.contributor.author
Cazzamalli, Samuele
dc.contributor.author
De Luca, Roberto
dc.contributor.author
Kerschenmeyer, Anne
dc.contributor.author
Valet, Philippe
dc.contributor.author
Villa, Alessandra
dc.contributor.author
Neri, Dario
dc.contributor.author
Matasci, Mattia
dc.date.accessioned
2021-04-13T09:55:43Z
dc.date.available
2021-04-11T02:57:08Z
dc.date.available
2021-04-13T09:55:43Z
dc.date.issued
2021-04-01
dc.identifier.issn
1535-3699
dc.identifier.other
10.1177/1535370220981578
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/478127
dc.description.abstract
Interleukin-9 is a cytokine with multiple functions, including the ability to activate group 2 innate lymphoid cells, which has been postulated to be therapeutically active in mouse models of arthritis. Similarly, interleukin-9 has been suggested to play an important role in tumor immunity. Here, we describe the cloning, expression, and characterization of three fusion proteins based on murine interleukin-9 and the F8 antibody, specific to the alternatively spliced EDA domain of fibronectin. EDA is strongly expressed in cancer and in various arthritic conditions, while being undetectable in the majority of healthy organs. Interleukin-9-based fusion proteins with an irrelevant antibody specific to hen egg lysozyme served as negative control in our study. The fusion proteins were characterized by quantitative biodistribution analysis in tumor-bearing mice using radioiodinated protein preparations. The highest tumor uptake and best tumor:organ ratios were observed for a format, in which the interleukin-9 moiety was flanked by two units of the F8 antibody in single-chain Fv format. Biological activity of interleukin-9 was retained when the payload was fused to antibodies. However, the targeted delivery of interleukin-9 to the disease site resulted in a modest anti-tumor activity in three different murine models of cancer (K1735M2, CT26, and F9), while no therapeutic benefit was observed in a collagen induced model of arthritis. Collectively, these results confirm the possibility to deliver interleukin-9 to the site of disease but cast doubts about the alleged therapeutic activity of this cytokine in cancer and arthritis, which has been postulated in previous publications.
en_US
dc.language.iso
en
en_US
dc.publisher
SAGE
dc.subject
Tumor targeting
en_US
dc.subject
rheumatoid arthritis targeting
en_US
dc.subject
fibronectin
en_US
dc.subject
immunocytokines
en_US
dc.subject
interleukin-9
en_US
dc.subject
armed-antibody
en_US
dc.title
Antibody-based delivery of interleukin-9 to neovascular structures: Therapeutic evaluation in cancer and arthritis
en_US
dc.type
Journal Article
dc.date.published
2021-01-21
ethz.journal.title
Experimental Biology and Medicine
ethz.journal.volume
246
en_US
ethz.journal.issue
8
en_US
ethz.journal.abbreviated
Exp Biol Med
ethz.pages.start
940
en_US
ethz.pages.end
951
en_US
ethz.grant
Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
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
182003
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte Lebenswissenschaften
ethz.date.deposited
2021-04-11T02:57:12Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2021-04-13T09:55:52Z
ethz.rosetta.lastUpdated
2024-02-02T13:30:17Z
ethz.rosetta.versionExported
true
ethz.COinS
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