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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
MUTATIONS, DYNAMICS, MEMBRANES, LEPTIN, LIGAND-BINDING, ALPHA-INTERFERON, BINDING-AFFINITY, PROTEIN COMPLEXES, I INTERFERON-RECEPTOR, BIOLOGICAL-ACTIVITY

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Citation

Please use this url to cite or link to this publication:

Chicago
Garcin, Geneviève, Franciane Paul, Markus Staufenbiel, Yann Bordat, José Van Der Heyden, Stephan Wilmes, Guillaume Cartron, et al. 2014. “High Efficiency Cell-specific Targeting of Cytokine Activity.” Nature Communications 5.
APA
Garcin, G., Paul, F., Staufenbiel, M., Bordat, Y., Van Der Heyden, J., Wilmes, S., Cartron, G., et al. (2014). High efficiency cell-specific targeting of cytokine activity. NATURE COMMUNICATIONS, 5.
Vancouver
1.
Garcin G, Paul F, Staufenbiel M, Bordat Y, Van Der Heyden J, Wilmes S, et al. High efficiency cell-specific targeting of cytokine activity. NATURE COMMUNICATIONS. 2014;5.
MLA
Garcin, Geneviève, Franciane Paul, Markus Staufenbiel, et al. “High Efficiency Cell-specific Targeting of Cytokine Activity.” NATURE COMMUNICATIONS 5 (2014): n. pag. Print.
@article{4378178,
  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.},
  articleno    = {3016},
  author       = {Garcin, Genevi{\`e}ve and Paul, Franciane and Staufenbiel, Markus and Bordat, Yann and Van Der Heyden, Jos{\'e} and Wilmes, Stephan and Cartron, Guillaume and Apparailly, Florence and De Koker, Stefaan and Piehler, Jacob and Tavernier, Jan and Uz{\'e}, Gilles},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {9},
  title        = {High efficiency cell-specific targeting of cytokine activity},
  url          = {http://dx.doi.org/10.1038/ncomms4016},
  volume       = {5},
  year         = {2014},
}

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