Cytokine Fusion Proteins
AssigneesBiotech Rna Pharmaceuticals GmbH, TRON—Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Universität Stuttgart
InventorsUgur Sahin, Friederike Gieseke, Ronald Backer, Sebastian Kreiter, Roland Kontermann, Klaus Pfizenmaier, Sina Fellermaier, Dafne Müller
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Abstract
The present invention relates to cytokine fusion proteins and to nucleic acid molecules encoding such cytokine fusion proteins. The present invention further relates to cells, non-human organisms. pharmaceutical compositions and kits comprising the cytokine fusion proteins or the nucleic acid molecules encoding them, as well as to their use as medicaments.
Claims36
A cytokine fusion protein comprising (i) three extracellular domains or fragments or variants thereof of a first ligand of the tumor necrosis factor (TNF) superfamily forming a first homotrimer capable of binding to a receptor of the first ligand and (ii) three extracellular domains or fragments or variants thereof of a second ligand of the TNF superfamily forming a second homotrimer capable of binding to a receptor of the second ligand, wherein the first ligand and the second ligand are different, and wherein the first homotrimer and the second homotrimer are covalently linked, preferably via one or more peptide linkers.
A cytokine fusion protein comprising a first block comprising three extracellular domains or fragments or variants thereof of a first ligand of the tumor necrosis factor (TNF) superfamily which are covalently linked and a second block comprising three extracellular domains or fragments or variants thereof of a second ligand of the TNF superfamily which are covalently linked, wherein the first ligand and the second ligand are different, and wherein the first block and the second block are covalently linked.
A cytokine fusion protein comprising the extracellular domain or a fragment or variant thereof of a first ligand of the tumor necrosis factor (TNF) superfamily and the extracellular domain or a fragment or variant thereof of a second ligand of the TNF superfamily, wherein the first ligand and the second ligand are different, and wherein the extracellular domains or fragments or variants thereof are covalently linked.
The cytokine fusion protein according to any one of the foregoing claims, wherein the first ligand and the second ligand are selected from the group consisting of CD40L, CD27L, 4-1BBL, OX40L, APRIL, CD30L, EDA-A1, EDA-A2, FasL, GITRL, LIGHT, LT-alpha, TL1A, TNF-alpha, TRAIL, RANKL, and TWEAK, preferably from the group consisting of CD40L, CD27L, 4-1BBL, and OX40L.
The cytokine fusion protein according to any one of the foregoing claims, further comprising at least one label or tag allowing the detection and/or isolation of the cytokine fusion protein.
The cytokine fusion protein according to any one of the foregoing claims, further comprising one or more modifications increasing the stability of the cytokine fusion protein.
A nucleic acid molecule encoding a cytokine fusion protein according to any one of the foregoing claims or a subunit thereof.
Dependencies are inferred from the claim text.