PASylated interleukins

PASylated Cytokines

Cytokines, like interleukins and interferons as well as its antagonists, are secreted proteins which play a key role in inflammation and immunity. Due to their typically small size (5-20 kDa), they are quickly eliminated via renal clearance. PASylation® enables the generation of long-acting cytokines for the treatment of autoimmune diseases and cancer. Beside the half-life extension effect, the PAS moiety may decrease systemic side-effects, leading to improved safety while tumor accumulation via the EPR-effect may further enhance therapeutic efficacy.

  • Extended plasma half-life

    • Expanded hydrodynamic volume  leading to extended circulation time
    • Reduced injection frequencies
  • Tumor accumulation

    • Tumor targeting via the EPR effect
    • Enhanced therapeutic efficacy
  • Efficient & cheap production

    • Genetic fusion, no need for chemical conjugation
    • Compatible with various industry standard expression systems
  • Improved safety

    • Potentially reduced systemic toxicity

  • Related publications

    Powers N. E., Swartzwelter B., Marchetti C., de Graaf D. M., Lerchner A., Schlapschy M., Datar R., Binder U., Edwards C. K. 3rd, Skerra A., Dinarello C. A. (2019) PASylation of IL-1 Receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis. J. Biol. Chem. 295, 868 –882.

  • Xia Y., Schlapschy M., Morath V., Roeder N., Vogt E.I., Stadler D., Cheng X., Dittmer U., Sutter K., Heikenwalder M., Skerra A., Protzer U. (2018) PASylated interferon α efficiently suppresses hepatitis B virus and induces anti-HBs seroconversion in HBV-transgenic mice. Antiviral Res. 161, 134-143.

  • Nganou-Makamdop K., Billingsley J.M., Yaffe Z., O’Connor G., Tharp G.K., Ransier A., Laboune F., Matus-Nicodemos R., Lerner A., Gharu L., Robertson J.M., Ford M.L., Schlapschy M., Kuhn N., Lensch A., Lifson J., Nason M., Skerra A., Schreiber G., Bosinger S.E., Douek D.C. (2018) Type I IFN signaling blockade by a PASylated antagonist during chronic SIV infection suppresses specific inflammatory pathways but does not alter T cell activation or virus replication. PLoS Pathog. 14, e1007246.

  • Zvonova E. A., Ershov A. V., Ershova O.A., Sudomoina M. A., Degterev M. B., Poroshin G. N., Eremeev A. V., Karpov A. P., Vishnevsky A. Y., Goldenkova-Pavlova I. V., Petrov A. V., Ruchko S. V., Shuster A. M. (2017) PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity. Appl. Microbiol. Biotechnol. 101, 1975-1987.

  • Harari D., Kuhn N., Abramovich R., Sasson K., Zozulya AL., Smith P., Schlapschy M., Aharoni R., Köster M., Eilam R., Skerra A., Schreiber G. (2014) Enhanced in vivo efficacy of a type I interferon superagonist with extended plasma half-life in a mouse model of multiple sclerosis. J. Biol. Chem. 289, 29014-29029.