Fusokines involving cytokines with strongly reduced receptor binding affinities
The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.
1. A composition comprising a protein consisting of two cytokines and a linker,
wherein the cytokines are human chemokine (C motif) ligand (XCL1) and human interferon alpha 2 (IFNα2), and
the IFNα2 comprises a mutation that reduces binding activity to its receptor as compared to wild-type IFNα2,
and XCL1 is wild-type and provides cell-specific targeting that restores activity of the mutant IFNα2 on the targeted cells.
2. The composition of claim 1 , wherein the linker is one or more GSS repeats.
3. A method of stimulating an immune response in a cell, comprising contacting the cell with a composition comprising a protein consisting of a two cytokines and a linker,
wherein the cytokines are human XCL1 and human IFNα2, and
the IFNα2 has a mutation which provides reduced affinity for its receptor as compared to wild-type IFNα2 and XCL1 is wild-type and provides cell-specific targeting that restores activity of the mutant IFNα2 on the targeted cells.
4. The method of claim 3 , wherein the linker is one or more GSS repeats.