High efficiency cell-specific targeting of cytokine activity
DC Element | Wert | Sprache |
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dc.contributor.author | Garcin, Genevieve | |
dc.contributor.author | Paul, Franciane | |
dc.contributor.author | Staufenbiel, Markus | |
dc.contributor.author | Bordat, Yann | |
dc.contributor.author | Van der Heyden, Jose | |
dc.contributor.author | Wilmes, Stephan | |
dc.contributor.author | Cartron, Guillaume | |
dc.contributor.author | Apparailly, Florence | |
dc.contributor.author | De Koker, Stefaan | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Tavernier, Jan | |
dc.contributor.author | Uze, Gilles | |
dc.date.accessioned | 2021-12-23T16:22:53Z | - |
dc.date.available | 2021-12-23T16:22:53Z | - |
dc.date.issued | 2014 | |
dc.identifier.issn | 20411723 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14340 | - |
dc.description.abstract | Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This `activity-by-targeting' concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines. | |
dc.description.sponsorship | Fondation ARC; FWO-VlaanderenFWO; LabEx MabImprove; Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) [IWT80016]; IUAP [P6/36]; GROUP-ID MRP-UGent; European Community's Seventh Framework Programme [223608]; We thank Dr Claude Libert for the gift of the anti-TNFR1 nanobody nb96; the anti-GFP Nb was provided by the VIB Nb service facility. We thank Hella Kenneweg for protein production and purification; Dr Pascale Louis-Plence, Javier Hernandez and Laurence Zitvogel for helpful discussions; Dr Sandra Pellegrini, Anne Blangy, Johan Grooten and Ion Gresser for reading of the manuscript. FP is supported by a fellowship from the Fondation ARC and SDK by a postdoctoral grant from the FWO-Vlaanderen. We thank the LabEx MabImprove for its support. This work was supported in part by a grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) to SDK (IWT80016), by IUAP P6/36 and the GROUP-ID MRP-UGent to J.T. and by the European Community's Seventh Framework Programme under grant agreement 223608 to G.U. and J.P. | |
dc.language.iso | en | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation.ispartof | NATURE COMMUNICATIONS | |
dc.subject | ALPHA-INTERFERON | |
dc.subject | BINDING-AFFINITY | |
dc.subject | BIOLOGICAL-ACTIVITY | |
dc.subject | DYNAMICS | |
dc.subject | I INTERFERON-RECEPTOR | |
dc.subject | LEPTIN | |
dc.subject | LIGAND-BINDING | |
dc.subject | MEMBRANES | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | MUTATIONS | |
dc.subject | PROTEIN COMPLEXES | |
dc.subject | Science & Technology - Other Topics | |
dc.title | High efficiency cell-specific targeting of cytokine activity | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/ncomms4016 | |
dc.identifier.isi | ISI:000331083600002 | |
dc.description.volume | 5 | |
dc.contributor.orcid | 0000-0003-1762-084X | |
dc.contributor.orcid | 0000-0002-4112-710X | |
dc.contributor.orcid | 0000-0002-4150-5772 | |
dc.contributor.orcid | 0000-0001-9669-7057 | |
dc.contributor.orcid | 0000-0001-8616-6498 | |
dc.contributor.researcherid | O-6383-2019 | |
dc.contributor.researcherid | AAU-5489-2020 | |
dc.contributor.researcherid | D-8635-2016 | |
dc.contributor.researcherid | AAG-3636-2019 | |
dc.publisher.place | MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND | |
dcterms.isPartOf.abbreviation | Nat. Commun. | |
dcterms.oaStatus | Green Published, Bronze | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
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geprüft am 15.05.2024